Quantitative dose-response analysis of ethyl methanesulfonate genotoxicity in adult gpt-delta transgenic mice

The assumption that mutagens have linear dose–responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA‐reactive mutagen and carcinogen, exhibited sublinear or thresholded dose‐responses for LacZ mutation in transgenic Muta™Mouse and for micronucleus (MN) frequency i...

Full description

Saved in:
Bibliographic Details
Published inEnvironmental and molecular mutagenesis Vol. 55; no. 5; pp. 385 - 399
Main Authors Cao, Xuefei, Mittelstaedt, Roberta A., Pearce, Mason G., Allen, Bruce C., Soeteman-Hernández, Lya G., Johnson, George E., Bigger, C. Anita H., Heflich, Robert H.
Format Journal Article
LanguageEnglish
Published United States Blackwell Publishing Ltd 01.06.2014
Wiley Subscription Services, Inc
Subjects
Animals
benchmark dose
bilinear model
Bone marrow
DNA Damage - drug effects
DNA Damage - genetics
dose-response
Dose-Response Relationship, Drug
Escherichia coli Proteins - physiology
Ethyl Methanesulfonate - toxicity
gene mutation
Genotoxicity
gpt
Hypoxanthine Phosphoribosyltransferase - genetics
Lac Operon - genetics
Male
Membrane Proteins - genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
micronucleus
Micronucleus Tests
Mutagenicity
Mutagens
Mutagens - toxicity
Mutation
Mutation - genetics
Mutation Rate
NOGEL
Pentosyltransferases - physiology
Pig-a
Reticulocytes - drug effects
Spleen - drug effects
threshold
micronucleus
gene mutation
dose-response
benchmark dose
Pig-a
gpt
threshold
bilinear model
NOGEL
Online AccessGet full text

Cover

Abstract The assumption that mutagens have linear dose–responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA‐reactive mutagen and carcinogen, exhibited sublinear or thresholded dose‐responses for LacZ mutation in transgenic Muta™Mouse and for micronucleus (MN) frequency in CD1 mice (Gocke E and Müller L [2009]: Mutat Res 678:101–107). In order to explore variables in establishing genotoxicity dose–responses, we characterized the genotoxicity of EMS using gene mutation assays anticipated to have lower spontaneous mutant frequencies (MFs) than Muta™Mouse. Male gpt‐delta transgenic mice were treated daily for 28 days with 5 to 100 mg/kg EMS, and measurements were made on: (i) gpt MFs in liver, lung, bone marrow, kidney, small intestine, and spleen; and (ii) Pig‐a MFs in peripheral blood reticulocytes (RETs) and total red blood cells. MN induction also was measured in peripheral blood RETs. These data were used to calculate Points of Departure (PoDs) for the dose responses, i.e., no‐observed‐genotoxic‐effect‐levels (NOGELs), lower confidence limits of threshold effect levels (Td‐LCIs), and lower confidence limits of 10% benchmark response rates (BMDL10s). Similar PoDs were calculated from the published EMS dose–responses for LacZ mutation and CD1 MN induction. Vehicle control gpt and Pig‐a MFs were 13–40‐fold lower than published vehicle control LacZ MFs. In general, the EMS genotoxicity dose–responses in gpt‐delta mice had lower PoDs than those calculated from the Muta™Mouse and CD1 mouse data. Our results indicate that the magnitude and possibly the shape of mutagenicity dose responses differ between in vivo models, with lower PoDs generally detected by gene mutation assays with lower backgrounds. Environ. Mol. Mutagen. 55:385–399, 2014. © 2014 Wiley Periodicals, Inc.
AbstractList The assumption that mutagens have linear dose–responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA‐reactive mutagen and carcinogen, exhibited sublinear or thresholded dose‐responses for LacZ mutation in transgenic Muta™Mouse and for micronucleus (MN) frequency in CD1 mice (Gocke E and Müller L [2009]: Mutat Res 678:101–107). In order to explore variables in establishing genotoxicity dose–responses, we characterized the genotoxicity of EMS using gene mutation assays anticipated to have lower spontaneous mutant frequencies (MFs) than Muta™Mouse. Male gpt ‐delta transgenic mice were treated daily for 28 days with 5 to 100 mg/kg EMS, and measurements were made on: (i) gpt MFs in liver, lung, bone marrow, kidney, small intestine, and spleen; and (ii) Pig‐a MFs in peripheral blood reticulocytes (RETs) and total red blood cells. MN induction also was measured in peripheral blood RETs. These data were used to calculate Points of Departure (PoDs) for the dose responses, i.e., no‐observed‐genotoxic‐effect‐levels (NOGELs), lower confidence limits of threshold effect levels (Td‐LCIs), and lower confidence limits of 10% benchmark response rates (BMDL 10 s). Similar PoDs were calculated from the published EMS dose–responses for LacZ mutation and CD1 MN induction. Vehicle control gpt and Pig‐a MFs were 13–40‐fold lower than published vehicle control LacZ MFs. In general, the EMS genotoxicity dose–responses in gpt ‐delta mice had lower PoDs than those calculated from the Muta™Mouse and CD1 mouse data. Our results indicate that the magnitude and possibly the shape of mutagenicity dose responses differ between in vivo models, with lower PoDs generally detected by gene mutation assays with lower backgrounds. Environ. Mol. Mutagen. 55:385–399, 2014. © 2014 Wiley Periodicals, Inc.
The assumption that mutagens have linear dose-responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA-reactive mutagen and carcinogen, exhibited sublinear or thresholded dose-responses for LacZ mutation in transgenic Muta™Mouse and for micronucleus (MN) frequency in CD1 mice (Gocke E and Müller L [2009]: Mutat Res 678:101-107). In order to explore variables in establishing genotoxicity dose-responses, we characterized the genotoxicity of EMS using gene mutation assays anticipated to have lower spontaneous mutant frequencies (MFs) than Muta™Mouse. Male gpt-delta transgenic mice were treated daily for 28 days with 5 to 100 mg/kg EMS, and measurements were made on: (i) gpt MFs in liver, lung, bone marrow, kidney, small intestine, and spleen; and (ii) Pig-a MFs in peripheral blood reticulocytes (RETs) and total red blood cells. MN induction also was measured in peripheral blood RETs. These data were used to calculate Points of Departure (PoDs) for the dose responses, i.e., no-observed-genotoxic-effect-levels (NOGELs), lower confidence limits of threshold effect levels (Td-LCIs), and lower confidence limits of 10% benchmark response rates (BMDL10 s). Similar PoDs were calculated from the published EMS dose-responses for LacZ mutation and CD1 MN induction. Vehicle control gpt and Pig-a MFs were 13-40-fold lower than published vehicle control LacZ MFs. In general, the EMS genotoxicity dose-responses in gpt-delta mice had lower PoDs than those calculated from the Muta™Mouse and CD1 mouse data. Our results indicate that the magnitude and possibly the shape of mutagenicity dose responses differ between in vivo models, with lower PoDs generally detected by gene mutation assays with lower backgrounds.
The assumption that mutagens have linear dose–responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA‐reactive mutagen and carcinogen, exhibited sublinear or thresholded dose‐responses for LacZ mutation in transgenic Muta™Mouse and for micronucleus (MN) frequency in CD1 mice (Gocke E and Müller L [2009]: Mutat Res 678:101–107). In order to explore variables in establishing genotoxicity dose–responses, we characterized the genotoxicity of EMS using gene mutation assays anticipated to have lower spontaneous mutant frequencies (MFs) than Muta™Mouse. Male gpt‐delta transgenic mice were treated daily for 28 days with 5 to 100 mg/kg EMS, and measurements were made on: (i) gpt MFs in liver, lung, bone marrow, kidney, small intestine, and spleen; and (ii) Pig‐a MFs in peripheral blood reticulocytes (RETs) and total red blood cells. MN induction also was measured in peripheral blood RETs. These data were used to calculate Points of Departure (PoDs) for the dose responses, i.e., no‐observed‐genotoxic‐effect‐levels (NOGELs), lower confidence limits of threshold effect levels (Td‐LCIs), and lower confidence limits of 10% benchmark response rates (BMDL10s). Similar PoDs were calculated from the published EMS dose–responses for LacZ mutation and CD1 MN induction. Vehicle control gpt and Pig‐a MFs were 13–40‐fold lower than published vehicle control LacZ MFs. In general, the EMS genotoxicity dose–responses in gpt‐delta mice had lower PoDs than those calculated from the Muta™Mouse and CD1 mouse data. Our results indicate that the magnitude and possibly the shape of mutagenicity dose responses differ between in vivo models, with lower PoDs generally detected by gene mutation assays with lower backgrounds. Environ. Mol. Mutagen. 55:385–399, 2014. © 2014 Wiley Periodicals, Inc.
The assumption that mutagens have linear dose-responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA-reactive mutagen and carcinogen, exhibited sublinear or thresholded dose-responses for LacZ mutation in transgenic Muta(TM)Mouse and for micronucleus (MN) frequency in CD1 mice (Gocke E and Muller L [2009]: Mutat Res 678:101-107). In order to explore variables in establishing genotoxicity dose-responses, we characterized the genotoxicity of EMS using gene mutation assays anticipated to have lower spontaneous mutant frequencies (MFs) than Muta(TM)Mouse. Male gpt-delta transgenic mice were treated daily for 28 days with 5 to 100 mg/kg EMS, and measurements were made on: (i) gpt MFs in liver, lung, bone marrow, kidney, small intestine, and spleen; and (ii) Pig-a MFs in peripheral blood reticulocytes (RETs) and total red blood cells. MN induction also was measured in peripheral blood RETs. These data were used to calculate Points of Departure (PoDs) for the dose responses, i.e., no-observed-genotoxic-effect-levels (NOGELs), lower confidence limits of threshold effect levels (Td-LCIs), and lower confidence limits of 10% benchmark response rates (BMDL10s). Similar PoDs were calculated from the published EMS dose-responses for LacZ mutation and CD1 MN induction. Vehicle control gpt and Pig-a MFs were 13-40-fold lower than published vehicle control LacZ MFs. In general, the EMS genotoxicity dose-responses in gpt-delta mice had lower PoDs than those calculated from the Muta(TM)Mouse and CD1 mouse data. Our results indicate that the magnitude and possibly the shape of mutagenicity dose responses differ between in vivo models, with lower PoDs generally detected by gene mutation assays with lower backgrounds. Environ. Mol. Mutagen. 55:385-399, 2014. © 2014 Wiley Periodicals, Inc. [PUBLICATION ABSTRACT]
The assumption that mutagens have linear dose-responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA-reactive mutagen and carcinogen, exhibited sublinear or thresholded dose-responses for LacZ mutation in transgenic Muta(TM)Mouse and for micronucleus (MN) frequency in CD1 mice (Gocke E and Mueller L [2009]: Mutat Res 678:101-107). In order to explore variables in establishing genotoxicity dose-responses, we characterized the genotoxicity of EMS using gene mutation assays anticipated to have lower spontaneous mutant frequencies (MFs) than Muta(TM)Mouse. Male gpt-delta transgenic mice were treated daily for 28 days with 5 to 100 mg/kg EMS, and measurements were made on: (i) gpt MFs in liver, lung, bone marrow, kidney, small intestine, and spleen; and (ii) Pig-a MFs in peripheral blood reticulocytes (RETs) and total red blood cells. MN induction also was measured in peripheral blood RETs. These data were used to calculate Points of Departure (PoDs) for the dose responses, i.e., no-observed-genotoxic-effect-levels (NOGELs), lower confidence limits of threshold effect levels (Td-LCIs), and lower confidence limits of 10% benchmark response rates (BMDL sub(10)s). Similar PoDs were calculated from the published EMS dose-responses for LacZ mutation and CD1 MN induction. Vehicle control gpt and Pig-a MFs were 13-40-fold lower than published vehicle control LacZ MFs. In general, the EMS genotoxicity dose-responses in gpt-delta mice had lower PoDs than those calculated from the Muta(TM)Mouse and CD1 mouse data. Our results indicate that the magnitude and possibly the shape of mutagenicity dose responses differ between in vivo models, with lower PoDs generally detected by gene mutation assays with lower backgrounds. Environ. Mol. Mutagen. 55:385-399, 2014. copyright 2014 Wiley Periodicals, Inc.
The assumption that mutagens have linear dose-responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA-reactive mutagen and carcinogen, exhibited sublinear or thresholded dose-responses for LacZ mutation in transgenic Muta™Mouse and for micronucleus (MN) frequency in CD1 mice (Gocke E and Müller L [2009]: Mutat Res 678:101-107). In order to explore variables in establishing genotoxicity dose-responses, we characterized the genotoxicity of EMS using gene mutation assays anticipated to have lower spontaneous mutant frequencies (MFs) than Muta™Mouse. Male gpt-delta transgenic mice were treated daily for 28 days with 5 to 100 mg/kg EMS, and measurements were made on: (i) gpt MFs in liver, lung, bone marrow, kidney, small intestine, and spleen; and (ii) Pig-a MFs in peripheral blood reticulocytes (RETs) and total red blood cells. MN induction also was measured in peripheral blood RETs. These data were used to calculate Points of Departure (PoDs) for the dose responses, i.e., no-observed-genotoxic-effect-levels (NOGELs), lower confidence limits of threshold effect levels (Td-LCIs), and lower confidence limits of 10% benchmark response rates (BMDL10 s). Similar PoDs were calculated from the published EMS dose-responses for LacZ mutation and CD1 MN induction. Vehicle control gpt and Pig-a MFs were 13-40-fold lower than published vehicle control LacZ MFs. In general, the EMS genotoxicity dose-responses in gpt-delta mice had lower PoDs than those calculated from the Muta™Mouse and CD1 mouse data. Our results indicate that the magnitude and possibly the shape of mutagenicity dose responses differ between in vivo models, with lower PoDs generally detected by gene mutation assays with lower backgrounds.The assumption that mutagens have linear dose-responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA-reactive mutagen and carcinogen, exhibited sublinear or thresholded dose-responses for LacZ mutation in transgenic Muta™Mouse and for micronucleus (MN) frequency in CD1 mice (Gocke E and Müller L [2009]: Mutat Res 678:101-107). In order to explore variables in establishing genotoxicity dose-responses, we characterized the genotoxicity of EMS using gene mutation assays anticipated to have lower spontaneous mutant frequencies (MFs) than Muta™Mouse. Male gpt-delta transgenic mice were treated daily for 28 days with 5 to 100 mg/kg EMS, and measurements were made on: (i) gpt MFs in liver, lung, bone marrow, kidney, small intestine, and spleen; and (ii) Pig-a MFs in peripheral blood reticulocytes (RETs) and total red blood cells. MN induction also was measured in peripheral blood RETs. These data were used to calculate Points of Departure (PoDs) for the dose responses, i.e., no-observed-genotoxic-effect-levels (NOGELs), lower confidence limits of threshold effect levels (Td-LCIs), and lower confidence limits of 10% benchmark response rates (BMDL10 s). Similar PoDs were calculated from the published EMS dose-responses for LacZ mutation and CD1 MN induction. Vehicle control gpt and Pig-a MFs were 13-40-fold lower than published vehicle control LacZ MFs. In general, the EMS genotoxicity dose-responses in gpt-delta mice had lower PoDs than those calculated from the Muta™Mouse and CD1 mouse data. Our results indicate that the magnitude and possibly the shape of mutagenicity dose responses differ between in vivo models, with lower PoDs generally detected by gene mutation assays with lower backgrounds.
Author Allen, Bruce C.
Bigger, C. Anita H.
Pearce, Mason G.
Soeteman-Hernández, Lya G.
Mittelstaedt, Roberta A.
Cao, Xuefei
Johnson, George E.
Heflich, Robert H.
Author_xml – sequence: 1
  givenname: Xuefei
  surname: Cao
  fullname: Cao, Xuefei
  organization: U.S. Food and Drug Administration, National Center for Toxicological Research, Arkansas, Jefferson
– sequence: 2
  givenname: Roberta A.
  surname: Mittelstaedt
  fullname: Mittelstaedt, Roberta A.
  organization: U.S. Food and Drug Administration, National Center for Toxicological Research, Arkansas, Jefferson
– sequence: 3
  givenname: Mason G.
  surname: Pearce
  fullname: Pearce, Mason G.
  organization: U.S. Food and Drug Administration, National Center for Toxicological Research, Arkansas, Jefferson
– sequence: 4
  givenname: Bruce C.
  surname: Allen
  fullname: Allen, Bruce C.
  organization: Bruce Allen Consulting, North Carolina, Chapel Hill
– sequence: 5
  givenname: Lya G.
  surname: Soeteman-Hernández
  fullname: Soeteman-Hernández, Lya G.
  organization: Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
– sequence: 6
  givenname: George E.
  surname: Johnson
  fullname: Johnson, George E.
  organization: Institute of Life Science, College of Medicine, Swansea University, Wales, United Kingdom
– sequence: 7
  givenname: C. Anita H.
  surname: Bigger
  fullname: Bigger, C. Anita H.
  organization: Bigger Consulting, Florida, St. Augustine
– sequence: 8
  givenname: Robert H.
  surname: Heflich
  fullname: Heflich, Robert H.
  email: robert.heflich@fda.hhs.gov
  organization: U.S. Food and Drug Administration, National Center for Toxicological Research, Arkansas, Jefferson
BackLink https://www.ncbi.nlm.nih.gov/pubmed/24535894$$D View this record in MEDLINE/PubMed
BookMark eNqN0VtrFDEUAOAgFbutgr9AAr74Mmvul0dZ6lqoiqWibyE7k6mpmWQ7yWjn35tua4VFQQgcAt-5cM4ROIgpOgCeY7TECJHXblgSrDh7BBYYadUQotABWCClaSOEJofgKOcrhDBmmjwBh4RxypVmCzB8mmwsvtjifzjYpeya0eVtitlBG22Ys88w9dCVb3OAQw02ujyFPkVbHLx0MZV041tfZugjtN0UCrzclqZzoVhYRhtzRb6Fg2_dU_C4tyG7Z_fxGHx-e3KxetecfVyfrt6cNS1TgjVKc7ShvJcdwrIjxLbS4o2yRIqNIFSKVmLeYavrp1e9ZB3jvVAbJhCltqP0GLy6q7sd0_XkcjGDz60LoQ6fpmww51gQphX-D0pJHYcLVunLPXqVprEuaafq40TLql7cq2kzuM5sRz_YcTa_d_6nYzumnEfXPxCMzO05jRvM7pyVLvdouztVinWxPvwtoblL-OmDm_9Z2Jy83_M-F3fz4O343QhJJTdfPqzN-kJ_PWd4Zc7pLwDCvds
CitedBy_id crossref_primary_10_1016_j_mrgentox_2018_02_001
crossref_primary_10_1002_em_22077
crossref_primary_10_1002_em_21981
crossref_primary_10_1002_em_22058
crossref_primary_10_1093_toxsci_kfw028
crossref_primary_10_1002_em_22137
crossref_primary_10_1016_j_mrgentox_2017_02_003
crossref_primary_10_1007_s00204_023_03553_w
crossref_primary_10_1093_mutage_gev035
crossref_primary_10_1002_em_21932
crossref_primary_10_1111_bcpt_12806
crossref_primary_10_1039_C4TX00118D
crossref_primary_10_1093_mutage_gev039
crossref_primary_10_1016_j_mrgentox_2014_10_008
crossref_primary_10_3389_fphar_2024_1484111
crossref_primary_10_1186_s41021_016_0072_6
crossref_primary_10_3109_10408444_2016_1171294
crossref_primary_10_1007_s11356_022_21605_z
crossref_primary_10_1016_j_mrrev_2014_11_001
crossref_primary_10_1016_j_mrrev_2015_11_001
crossref_primary_10_1111_risa_13191
crossref_primary_10_5487_TR_2018_34_4_303
crossref_primary_10_1002_em_22151
Cites_doi 10.1073/pnas.86.20.7971
10.1016/j.toxlet.2009.03.021
10.1084/jem.177.2.517
10.3123/jemsge.31.105
10.1002/em.20667
10.1093/toxsci/66.2.298
10.1002/(SICI)1098-2280(1999)34:1<1::AID-EM1>3.0.CO;2-P
10.1093/toxsci/kfq341
10.1002/(SICI)1098-2280(1996)28:4<465::AID-EM24>3.0.CO;2-C
10.1016/j.mrgentox.2003.07.004
10.1080/15287391003689234
10.1002/em.20654
10.1073/pnas.86.22.8620
10.1086/100259
10.1016/j.toxlet.2004.04.004
10.1007/978-1-4899-0301-3_29
10.1073/pnas.96.9.5209
10.1016/j.mrrev.2005.04.002
10.1002/em.20414
10.1016/j.mrgentox.2011.06.005
10.1016/j.toxlet.2009.03.016
10.1016/j.mrgentox.2008.08.011
10.1002/em.20627
10.18637/jss.v034.i02
10.1016/0165-1110(84)90007-1
10.1002/em.20413
10.1093/mutage/14.1.113
10.1016/j.toxlet.2009.03.027
10.1016/S0027-5107(98)00147-X
10.1016/j.mrgentox.2011.03.016
10.1016/S0027-5107(00)00077-4
10.1002/em.20682
10.1093/toxsci/kfs341
10.1002/em.20379
10.1016/0165-1218(89)90089-X
10.1016/S0027-5107(99)00208-0
10.1016/0165-1161(94)90053-1
10.1007/978-1-62703-529-3_5
10.1016/0735-0651(90)90003-X
10.1016/j.mrgentox.2013.03.002
10.1016/j.mrgentox.2009.05.010
10.1016/j.mrgentox.2009.04.005
10.1016/j.toxlet.2009.04.031
10.1016/0027-5107(70)90049-7
10.1016/j.toxlet.2009.03.015
10.1016/j.mrfmmm.2003.11.009
10.1002/(SICI)1098-2280(2000)35:3<253::AID-EM11>3.0.CO;2-J
10.1073/pnas.90.22.10681
10.1016/S1383-5718(99)00161-8
10.1016/j.toxlet.2009.03.008
10.1002/em.21727
10.1016/j.mrgentox.2009.05.009
ContentType Journal Article
Copyright Copyright © 2014 Wiley Periodicals, Inc.
Copyright_xml – notice: Copyright © 2014 Wiley Periodicals, Inc.
DBID BSCLL
AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
7ST
7TM
7U7
8FD
C1K
FR3
P64
RC3
SOI
7X8
DOI 10.1002/em.21854
DatabaseName Istex
CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
Environment Abstracts
Nucleic Acids Abstracts
Toxicology Abstracts
Technology Research Database
Environmental Sciences and Pollution Management
Engineering Research Database
Biotechnology and BioEngineering Abstracts
Genetics Abstracts
Environment Abstracts
MEDLINE - Academic
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Genetics Abstracts
Technology Research Database
Toxicology Abstracts
Nucleic Acids Abstracts
Engineering Research Database
Environment Abstracts
Biotechnology and BioEngineering Abstracts
Environmental Sciences and Pollution Management
MEDLINE - Academic
DatabaseTitleList CrossRef
MEDLINE

Genetics Abstracts
Genetics Abstracts
MEDLINE - Academic
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
EISSN 1098-2280
EndPage 399
ExternalDocumentID 3322907541
24535894
10_1002_em_21854
EM21854
ark_67375_WNG_GT9XR41C_R
Genre article
Research Support, Non-U.S. Gov't
Journal Article
GrantInformation_xml – fundername: Commissioner's Fellowship Program of the U.S. FDA
GroupedDBID ---
.3N
.GA
.Y3
05W
0R~
10A
1L6
1OB
1OC
1ZS
31~
33P
3SF
3WU
4.4
50Y
50Z
51W
51X
52M
52N
52O
52P
52R
52S
52T
52U
52V
52W
52X
53G
5GY
5VS
66C
702
7PT
8-0
8-1
8-3
8-4
8-5
8UM
930
A01
A03
A8Z
AAESR
AAEVG
AAHHS
AAIKC
AAMNW
AANLZ
AAONW
AASGY
AAXRX
AAZKR
ABCQN
ABCUV
ABEFU
ABEML
ABIJN
ABJNI
ABPVW
ABQWH
ABXGK
ACAHQ
ACBWZ
ACCFJ
ACCZN
ACGFS
ACGOF
ACMXC
ACPOU
ACPRK
ACSCC
ACXBN
ACXQS
ADBBV
ADBTR
ADEOM
ADIZJ
ADKYN
ADMGS
ADOZA
ADXAS
ADZMN
ADZOD
AEEZP
AEIGN
AEIMD
AENEX
AEQDE
AEUQT
AEUYR
AFBPY
AFFPM
AFGKR
AFPWT
AFRAH
AFZJQ
AHBTC
AI.
AIACR
AITYG
AIURR
AIWBW
AJBDE
ALAGY
ALMA_UNASSIGNED_HOLDINGS
ALUQN
AMBMR
AMYDB
ASPBG
ATUGU
AVWKF
AZBYB
AZFZN
AZVAB
BAFTC
BDRZF
BFHJK
BHBCM
BMXJE
BROTX
BRXPI
BSCLL
BY8
C45
CS3
D-6
D-7
D-E
D-F
DCZOG
DPXWK
DR2
DRFUL
DRMAN
DRSTM
DU5
DUUFO
EBD
EBS
EDH
EJD
EMOBN
ESTFP
F00
F01
F04
F5P
FEDTE
FUBAC
G-S
G.N
GNP
GODZA
H.X
HBH
HF~
HGLYW
HHY
HHZ
HVGLF
HZ~
IX1
J0M
JPC
KBYEO
KQQ
LATKE
LAW
LC2
LC3
LEEKS
LITHE
LOXES
LP6
LP7
LUTES
LYRES
MEWTI
MK4
MRFUL
MRMAN
MRSTM
MSFUL
MSMAN
MSSTM
MXFUL
MXMAN
MXSTM
N04
N05
N9A
NF~
NNB
O66
O9-
OIG
OVD
P2P
P2W
P2X
P2Z
P4B
P4D
PALCI
PQQKQ
Q.N
Q11
QB0
QRW
R.K
RIWAO
RJQFR
ROL
RWI
RX1
SAMSI
SUPJJ
SV3
TEORI
TN5
UB1
V2E
VH1
W8V
W99
WBKPD
WIB
WIH
WIJ
WIK
WJL
WNSPC
WOHZO
WQJ
WRC
WUP
WWO
WXI
WXSBR
WYISQ
XG1
XV2
ZGI
ZXP
ZZTAW
~IA
~KM
~WT
AAHQN
AAIPD
AAMNL
AANHP
AAYCA
ACRPL
ACYXJ
ADNMO
AFWVQ
ALVPJ
AAYXX
AEYWJ
AGHNM
AGQPQ
AGYGG
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
7ST
7TM
7U7
8FD
AAMMB
AEFGJ
AGXDD
AIDQK
AIDYY
C1K
FR3
P64
RC3
SOI
7X8
ID FETCH-LOGICAL-c4864-8950b35f7d017d22ac7a1b8a276b62376c715d1a9623f8f74d45f68b46033ad33
IEDL.DBID DR2
ISSN 0893-6692
1098-2280
IngestDate Thu Jul 10 18:11:59 EDT 2025
Fri Jul 11 02:52:02 EDT 2025
Fri Jul 25 10:34:41 EDT 2025
Thu Apr 03 06:58:15 EDT 2025
Thu Apr 24 22:56:24 EDT 2025
Tue Jul 01 00:43:31 EDT 2025
Wed Jan 22 16:36:30 EST 2025
Wed Oct 30 09:51:10 EDT 2024
IsPeerReviewed true
IsScholarly true
Issue 5
Keywords micronucleus
gene mutation
dose-response
benchmark dose
Pig-a
gpt
threshold
bilinear model
NOGEL
Language English
License http://onlinelibrary.wiley.com/termsAndConditions#vor
Copyright © 2014 Wiley Periodicals, Inc.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c4864-8950b35f7d017d22ac7a1b8a276b62376c715d1a9623f8f74d45f68b46033ad33
Notes ArticleID:EM21854
ark:/67375/WNG-GT9XR41C-R
Commissioner's Fellowship Program of the U.S. FDA
istex:7F2F6852319A93F253F6B4167E90A82520A50D1F
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
PMID 24535894
PQID 1531535297
PQPubID 105685
PageCount 15
ParticipantIDs proquest_miscellaneous_1551624981
proquest_miscellaneous_1532950564
proquest_journals_1531535297
pubmed_primary_24535894
crossref_primary_10_1002_em_21854
crossref_citationtrail_10_1002_em_21854
wiley_primary_10_1002_em_21854_EM21854
istex_primary_ark_67375_WNG_GT9XR41C_R
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate June 2014
PublicationDateYYYYMMDD 2014-06-01
PublicationDate_xml – month: 06
  year: 2014
  text: June 2014
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: Reston
PublicationTitle Environmental and molecular mutagenesis
PublicationTitleAlternate Environ. Mol. Mutagen
PublicationYear 2014
Publisher Blackwell Publishing Ltd
Wiley Subscription Services, Inc
Publisher_xml – name: Blackwell Publishing Ltd
– name: Wiley Subscription Services, Inc
References Sega GA. 1984. A review of the genetic effects of EMS. Mutat Res 134:113-142.
Johnson GE, Doak SH, Griffiths SM, Quick EL, Skibinski DOF, Azir ZM, Jenkins GJ. 2009. Non-linear dose-response of DNA-reactive genotoxins: Recommendations for data analysis. Mutat Res 678:95-100.
Slob W. 2002. Dose-response modeling of continuous endpoints. Toxicol Sci 66:298-312.
Manjanatha MG, Shelton SD, Bishop M, Shaddock JG, Dobrovolsky VN, Heflich RH, Webb PJ, Blankenship LR, Beland FA, Greenlees KJ, et al. 2004. Analysis of mutations and bone marrow micronuclei in Big Blue® rats fed leucomalachite green. Mutat Res 547:5-18.
Nohmi T, Katoh M, Suzuki H, Matsui M, Tamada M, Watanabe M, Suzuki M, Horiya N, Ueda O, Shibuya T, et al. 1996. A new transgenic mouse mutagenesis test system using Spi- and 6-thioguanine selections. Environ Mol Mutagen 28:465-470.
Masumura K, Matsui M, Katoh M, Horiya N, Ueda O, Tanabe H, Yamada M, Suzuki H, Sofuni T, Nohmi T. 1999. Spectra of gpt mutations in ethylnitrosourea-treated and untreated transgenic mice. Environ Mol Mutagen 34:1-8.
European Food Safety Authority (EFSA). 2009. Guidance of the scientific committee on a request from EFSA on the use of the benchmark dose approach in risk assessment. EFSA J 1150:1-72.
Bolt HM, Foth H, Hengstler JG, Degen GH. 2004. Carcinogenicity categorization of chemicals-new aspects to be considered in a European perspective. Toxicol Lett 151:29-41.
Gollapudi BB, Johnson GE, Hernandez LG, Pottenger LH, Dearfield KL, Jeffery AM, Julien E, Kim JH, Lovell DP, MacGregor JT, et al. 2013. Quantitative approaches for assessing dose-response relationships in gentic toxicology studies. Environ Mol Mugagen 54:8-18.
Müller L, Gocke E. 2009. Considerations regarding a permitted daily exposure calculation for ethyl methanesulfonate. Toxicol Lett 190:330-332.
Trentin GA, Moody J, Heddle JA. 1998. Effect of maternal folate levels on somatic mutation frequency in the developing colon. Mutat Res 405:81-87.
Gocke E, Burgin H, Müller L, Phister T. 2009b. Literature review on the genotoxicity, reproductive toxicity, and carcinogenicity of ethyl methanesulfonate. Toxicol Lett 190:254-265.
Masumura K. 2009. Spontaneous and induced gpt and Spi- mutant frequencies in gpt delta transgenic rodents. Gene Environ 31:105-118.
Yang Y, Allen BC, Tan Y-M, Liao KH, Clewell III HJ. 2010. Bayesian analysis of a rat formaldehyde DNA-protein cross-link model. J Toxicol Environ Health A 73:787-806.
Gocke E, Wall M. 2009. In vivo genotoxicity of EMS: Statistical assessment of the dose response curves. Toxicol Lett 190:298-302.
Cosentino L, Heddle JA. 1999. A comparison of the effects of diverse mutagens at the LacZ transgene and Dlb-1 locus in vivo. Mutagenesis 14:113-119.
Kohler SW, Provost GS, Kretz PL, Fieck A, Sorge JA, Short JM. 1990. The use of transgenic mice for short-term, in vivo mutagenicity testing. Genet Anal Tech Appl (GATA) 7:212-218.
Lutz WK, Lutz RW. 2009. Statistical model to estimate threshold dose and its confidence limits for the analysis of sublinear dose-response relationships, exemplified for mutagenicity data. Mutat Res 678:118-122.
Tao KS, Urlando C, Heddle JA. 1993. Comparison of somatic mutation in a transgenic versus host locus. Proc Natl Acad Sci USA 90:10681-10685.
Miura D, Shaddock JG, Mittelstaedt RA, Dobrovolsky VN, Kimoto T, Kasahara Y, Heflich RH. 2011. Analysis of mutations in the Pig-a gene of spleen T-cells from N-ethyl-N-nitrosourea-treated Fisher 344 rats. Environ Mol Mutagen 52:419-423.
Cribari-Neto F, Zeileis A. 2010. Beta regression in R. J Stat Software 34:1-24.
Bhalli JA, Ding W, Shaddock JG, Pearce MG, Dobrovolsky VN, Heflich RH. 2013. Evaluating the weak in vivo micronucleus response of a genotoxic carcinogen, Aristolochic acids. Mutat Res 753:82-92.
Dobrovolsky, VN, Elespuru RK, Bigger CAH, Robinson TW, Heflich RH. 2011. Monitoring humans for somatic mutation in the endogenous PIG-A gene using red blood cells. Environ Mol Mutagen 52:784-794.
Robinson DR, Goodall K, Albertini RJ, O'Neill JP, Finette B, Sala-Trepat M, Moustacchi E, Tates AD, Beare DM, Green MHL, et al. 1994. An analysis of the in vivo hprt mutant frequency in circulating T-lymphocytes in the normal human population: a comparison of four datasets. Mutat Res 313:227-247.
Gossen JA, de Leeuw WJF, Tan CHT, Zwarthoff EC, Berends F, Lohman PHM, Knook DL, Vijg J. 1989. Efficient rescue of integrated shuttle vectors from transgenic mice: A model for studying mutations in vivo. Proc Natl Acad Sci USA 86:7971-7975.
Kirsch-Volders M, Aardema M, Elhajouji A. 2000. Concepts of threshold in mutagenesis and carcinogenesis. Mutat Res 464:3-11.
Peirce B. 1852. Criterion for the rejection of doubtful observations. Astronomical J 2:161-163.
Miura D, Dobrovolsky VN, Mittelstaedt RA, Kasahara Y, Katsuura Y, Heflich RH. 2008b. Development of an in vivo gene mutation assay using the endogenous Pig-A gene: II. Selection of Pig-A mutant rat spleen T-cells with proaerolysin and sequencing Pig-A cDNA from the mutants. Environ Mol Mutagen 49:622-630.
Takahashi M, Takeda J, Hirose S, Hyman R, Inoue N, Miyata T, Ueda E, Kitani T, Medof ME, Kinoshita T. 1993. Deficient biosynthesis of N-acetylglucosaminyl-phospatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor biosynthesis, in cell lines established from patients with Paroxysmal Nocturnal Hemoglobinuria. J Exp Med 177:517-521.
Gocke E, Ballantyne M, Whitwell J, Müller L. 2009a. MNT and Muta™Mouse studies to define the in vivo dose response relations of the genotoxicity of EMS and ENU. Toxicol Lett 190:287-297.
Walker VE, Casciano DA, Tweats DJ. 2009. The Viracept-EMS case: Impact and outlook. Toxicol Lett 190:333-339.
Bryce SM, Bemis JC, Dertinger SD. 2008. In vivo mutation assay based on the endogenous Pig-a locus. Environ Mol Mutagen 49:256-264.
Phonethepswath S, Bryce SM, Bemis JC, Dertinger SD. 2008. Erythrocyte-based Pig-a gene mutation assay: Demonstration of cross-species potential. Mutat Res 657:122-126.
van Sittert NJ, Boogaard PJ, Natarajan AT, Tates AD, Ehrenberg LG, Tornqvist MA. 2000. Formation of DNA adducts and induction of mutagenic effects in rats following 4 weeks inhalation exposure to ethylene oxide as a basis for cancer risk assessment. Mutat Res 447:27-48.
Thomas AD, Jenkins GJS, Kaina B, Bodger O, Tomaszowaki K-H, Lewis PD, Doak SH, Johnson GE. 2013. Influence of DNA repair on nonlinear dose-responses for mutation. Toxicol Sci 132:87-95.
Heddle JA, Dean S, Nohmi T, Boerrigter M, Casciano D, Douglas GR, Glickman BW, Gorelick NJ, Mirsalis JC, Martus H-J, et al. 2000. In vivo transgenic mutation assays. Environ Mol Mutagen 35:253-259.
Nohmi T, Suzuki T, Masumura K-i. 2000. Recent advances in the protocols of transgenic mouse mutation assays. Mutat Res 455:191-215.
Ellison KS, Dogliotti E, Connors TD, Basu AK, Essigmann JM. 1989. Site-specific mutagenesis by O6-alkylguanines located in the chromosomes of mammalian cells: Influence of the mammalian O6-alkylguanine-DNA alkyltransferase. Proc Natl Acad Sci USA 86:8620-8624.
Gocke E, Müller L. 2009. In vivo studies in the mouse to define a threshold for the genotoxicity of EMS and ENU. Mutat Res 678:101-107.
Araten DJ, Nafa K, Pakdeesuwan K, Luzzatto L. 1999. Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. Proc Natl Acad Sci USA 96:5209-5214.
Dobrovolsky VN, Miura D, Heflich RH, Dertinger SD. 2010. The in vivo Pig-a gene mutation assay, a potential tool for regulatory safety assessment. Environ Mol Mutagen 51:825-835.
Kondo K, Suzuki H, Hoshi K, Yasui H. 1989. Micronucleus test with ethyl methanesulfonate administered by intraperitoneal injection and oral gavage. Mutat Res 223:373-375.
Zair ZM, Jenkins GJ, Doak SH, Singh R, Brown K, Johnson GE. 2011. N-Methylpurine DNA glycosylase plays a pivotal role in the threshold response of ethylmethansulfonate-induced chromosome damage. Toxicol Sci 119:346-358.
Zito R. 2001. Low doses and thresholds in genotoxicity: From theories to experiments. J Exp Clin Cancer Res 20:315-325.
Bhalli JA, Pearce MG, Dobrovolsky VN, Heflich RH. 2011. Manifestation and persistence of Pig-a mutant red blood cells in C57BL/6 mice following single and split doses of N-ethyl-N-nitrosourea. Environ Mol Mutagen 52:766-773.
Dobo KL, Fiedler RD, Gunther WC, Thiffeault CJ, Cammerer Z, Coffing SL, Shutsky T, Schuler M. 2011. Defining EMS and ENU dose-response relationships using the Pig-a mutation assay in rats. Mutat Res 725:13-21.
Kimoto T, Suzuki K, Kobayashi Xm, Dobrovolsky VN, Heflich RH, Miura D, Kasahara Y. 2011. Manifestation of Pig-a mutant bone marrow erythroids and peripheral blood erythrocytes in mice treated with N-ethyl-N-nitrosourea: Direct sequencing of Pig-a cDNA from bone marrow cells negative for GPI-anchored protein expression. Mutat Res 723:36-42.
Pfister T, Eichinger-Chapelon A. 2009. General 4-week toxicity study with EMS in the rat. Toxicol Lett 190:271-285.
Cumming RB, Walton MF. 1970. Fate and metabolism of some mutagenic alkylating agents in the mouse. I. Ethyl methanesulfonate and methyl methanesulfonate at sublethal dose in hybrid males. Mutat Res 10:365-377.
Lambert IB, Singer TM, Boucher SE, Douglas GR. 2005. Detailed review of transgenic rodent mutation assays. Mutat Res 590:1-280.
Miura D, Dobrovolsky VN, Kasahara Y, Katsuura Y, Heflich RH. 2008a. Development of an in vivo gene mutation assay using the endogenous Pig-A gene: I. Flow cytometric detection of CD59-negative peripheral red blood cells and CD48-negative spleen T-cells from the rat. Environ Mol Mutagen 49:614-621.
Thybaud V, Dean S, Nohmi T, de Boer J, Douglas GR, Glickman BW, Gorelick NJ, Heddle JA, Heflich RH, Lambert I, et al. 2003. In vivo transgenic mutation assays. Mutat Res 540:141-151.
2011; 119
1989; 86
2000; 455
1987; 7
2011; 52
2009a; 190
2009; 678
2011; 725
1996; 28
2011; 723
2008a; 49
2013; 1044
2013; 54
1989; 223
1852; 2
2000; 447
2013; 753
1999; 14
1998; 405
1999; 96
2008b; 49
2009; 1150
2009b; 190
2010; 73
1993; 177
2010; 34
2005; 590
1994; 313
2012
2011
2009
1970; 10
1996
2006
1993; 90
2004; 547
2001; 20
2009; 31
2009; 190
1984; 134
2000; 35
2004; 151
2008; 49
2002; 66
1999; 34
2008; 657
2013; 132
2000; 464
1990; 7
2003; 20
2003; 540
2010; 51
e_1_2_7_5_1
e_1_2_7_3_1
e_1_2_7_9_1
e_1_2_7_7_1
e_1_2_7_19_1
e_1_2_7_60_1
e_1_2_7_17_1
e_1_2_7_15_1
e_1_2_7_41_1
e_1_2_7_43_1
e_1_2_7_11_1
e_1_2_7_45_1
e_1_2_7_47_1
e_1_2_7_26_1
e_1_2_7_28_1
e_1_2_7_50_1
e_1_2_7_25_1
e_1_2_7_31_1
e_1_2_7_52_1
e_1_2_7_23_1
e_1_2_7_33_1
e_1_2_7_54_1
e_1_2_7_21_1
e_1_2_7_35_1
e_1_2_7_56_1
e_1_2_7_37_1
e_1_2_7_58_1
e_1_2_7_39_1
Sega GA. (e_1_2_7_49_1) 1984; 134
e_1_2_7_6_1
European Food Safety Authority (EFSA) (e_1_2_7_13_1) 2009; 1150
e_1_2_7_4_1
Zito R. (e_1_2_7_61_1) 2001; 20
e_1_2_7_8_1
e_1_2_7_18_1
e_1_2_7_16_1
e_1_2_7_40_1
e_1_2_7_2_1
e_1_2_7_14_1
e_1_2_7_42_1
e_1_2_7_12_1
e_1_2_7_44_1
e_1_2_7_10_1
e_1_2_7_46_1
e_1_2_7_48_1
e_1_2_7_27_1
e_1_2_7_29_1
e_1_2_7_51_1
e_1_2_7_30_1
e_1_2_7_53_1
e_1_2_7_24_1
e_1_2_7_32_1
e_1_2_7_55_1
e_1_2_7_22_1
e_1_2_7_34_1
e_1_2_7_57_1
e_1_2_7_20_1
e_1_2_7_36_1
e_1_2_7_59_1
e_1_2_7_38_1
References_xml – reference: Gollapudi BB, Johnson GE, Hernandez LG, Pottenger LH, Dearfield KL, Jeffery AM, Julien E, Kim JH, Lovell DP, MacGregor JT, et al. 2013. Quantitative approaches for assessing dose-response relationships in gentic toxicology studies. Environ Mol Mugagen 54:8-18.
– reference: Dobrovolsky, VN, Elespuru RK, Bigger CAH, Robinson TW, Heflich RH. 2011. Monitoring humans for somatic mutation in the endogenous PIG-A gene using red blood cells. Environ Mol Mutagen 52:784-794.
– reference: Pfister T, Eichinger-Chapelon A. 2009. General 4-week toxicity study with EMS in the rat. Toxicol Lett 190:271-285.
– reference: Sega GA. 1984. A review of the genetic effects of EMS. Mutat Res 134:113-142.
– reference: Johnson GE, Doak SH, Griffiths SM, Quick EL, Skibinski DOF, Azir ZM, Jenkins GJ. 2009. Non-linear dose-response of DNA-reactive genotoxins: Recommendations for data analysis. Mutat Res 678:95-100.
– reference: Kohler SW, Provost GS, Kretz PL, Fieck A, Sorge JA, Short JM. 1990. The use of transgenic mice for short-term, in vivo mutagenicity testing. Genet Anal Tech Appl (GATA) 7:212-218.
– reference: Zair ZM, Jenkins GJ, Doak SH, Singh R, Brown K, Johnson GE. 2011. N-Methylpurine DNA glycosylase plays a pivotal role in the threshold response of ethylmethansulfonate-induced chromosome damage. Toxicol Sci 119:346-358.
– reference: Bhalli JA, Ding W, Shaddock JG, Pearce MG, Dobrovolsky VN, Heflich RH. 2013. Evaluating the weak in vivo micronucleus response of a genotoxic carcinogen, Aristolochic acids. Mutat Res 753:82-92.
– reference: Masumura K. 2009. Spontaneous and induced gpt and Spi- mutant frequencies in gpt delta transgenic rodents. Gene Environ 31:105-118.
– reference: Phonethepswath S, Bryce SM, Bemis JC, Dertinger SD. 2008. Erythrocyte-based Pig-a gene mutation assay: Demonstration of cross-species potential. Mutat Res 657:122-126.
– reference: Walker VE, Casciano DA, Tweats DJ. 2009. The Viracept-EMS case: Impact and outlook. Toxicol Lett 190:333-339.
– reference: Yang Y, Allen BC, Tan Y-M, Liao KH, Clewell III HJ. 2010. Bayesian analysis of a rat formaldehyde DNA-protein cross-link model. J Toxicol Environ Health A 73:787-806.
– reference: Gocke E, Ballantyne M, Whitwell J, Müller L. 2009a. MNT and Muta™Mouse studies to define the in vivo dose response relations of the genotoxicity of EMS and ENU. Toxicol Lett 190:287-297.
– reference: Kondo K, Suzuki H, Hoshi K, Yasui H. 1989. Micronucleus test with ethyl methanesulfonate administered by intraperitoneal injection and oral gavage. Mutat Res 223:373-375.
– reference: Miura D, Shaddock JG, Mittelstaedt RA, Dobrovolsky VN, Kimoto T, Kasahara Y, Heflich RH. 2011. Analysis of mutations in the Pig-a gene of spleen T-cells from N-ethyl-N-nitrosourea-treated Fisher 344 rats. Environ Mol Mutagen 52:419-423.
– reference: Cumming RB, Walton MF. 1970. Fate and metabolism of some mutagenic alkylating agents in the mouse. I. Ethyl methanesulfonate and methyl methanesulfonate at sublethal dose in hybrid males. Mutat Res 10:365-377.
– reference: Ellison KS, Dogliotti E, Connors TD, Basu AK, Essigmann JM. 1989. Site-specific mutagenesis by O6-alkylguanines located in the chromosomes of mammalian cells: Influence of the mammalian O6-alkylguanine-DNA alkyltransferase. Proc Natl Acad Sci USA 86:8620-8624.
– reference: Gossen JA, de Leeuw WJF, Tan CHT, Zwarthoff EC, Berends F, Lohman PHM, Knook DL, Vijg J. 1989. Efficient rescue of integrated shuttle vectors from transgenic mice: A model for studying mutations in vivo. Proc Natl Acad Sci USA 86:7971-7975.
– reference: Thybaud V, Dean S, Nohmi T, de Boer J, Douglas GR, Glickman BW, Gorelick NJ, Heddle JA, Heflich RH, Lambert I, et al. 2003. In vivo transgenic mutation assays. Mutat Res 540:141-151.
– reference: Tao KS, Urlando C, Heddle JA. 1993. Comparison of somatic mutation in a transgenic versus host locus. Proc Natl Acad Sci USA 90:10681-10685.
– reference: Miura D, Dobrovolsky VN, Mittelstaedt RA, Kasahara Y, Katsuura Y, Heflich RH. 2008b. Development of an in vivo gene mutation assay using the endogenous Pig-A gene: II. Selection of Pig-A mutant rat spleen T-cells with proaerolysin and sequencing Pig-A cDNA from the mutants. Environ Mol Mutagen 49:622-630.
– reference: Masumura K, Matsui M, Katoh M, Horiya N, Ueda O, Tanabe H, Yamada M, Suzuki H, Sofuni T, Nohmi T. 1999. Spectra of gpt mutations in ethylnitrosourea-treated and untreated transgenic mice. Environ Mol Mutagen 34:1-8.
– reference: Bryce SM, Bemis JC, Dertinger SD. 2008. In vivo mutation assay based on the endogenous Pig-a locus. Environ Mol Mutagen 49:256-264.
– reference: Araten DJ, Nafa K, Pakdeesuwan K, Luzzatto L. 1999. Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. Proc Natl Acad Sci USA 96:5209-5214.
– reference: Zito R. 2001. Low doses and thresholds in genotoxicity: From theories to experiments. J Exp Clin Cancer Res 20:315-325.
– reference: Thomas AD, Jenkins GJS, Kaina B, Bodger O, Tomaszowaki K-H, Lewis PD, Doak SH, Johnson GE. 2013. Influence of DNA repair on nonlinear dose-responses for mutation. Toxicol Sci 132:87-95.
– reference: Miura D, Dobrovolsky VN, Kasahara Y, Katsuura Y, Heflich RH. 2008a. Development of an in vivo gene mutation assay using the endogenous Pig-A gene: I. Flow cytometric detection of CD59-negative peripheral red blood cells and CD48-negative spleen T-cells from the rat. Environ Mol Mutagen 49:614-621.
– reference: Gocke E, Burgin H, Müller L, Phister T. 2009b. Literature review on the genotoxicity, reproductive toxicity, and carcinogenicity of ethyl methanesulfonate. Toxicol Lett 190:254-265.
– reference: Nohmi T, Suzuki T, Masumura K-i. 2000. Recent advances in the protocols of transgenic mouse mutation assays. Mutat Res 455:191-215.
– reference: Bolt HM, Foth H, Hengstler JG, Degen GH. 2004. Carcinogenicity categorization of chemicals-new aspects to be considered in a European perspective. Toxicol Lett 151:29-41.
– reference: Gocke E, Müller L. 2009. In vivo studies in the mouse to define a threshold for the genotoxicity of EMS and ENU. Mutat Res 678:101-107.
– reference: Peirce B. 1852. Criterion for the rejection of doubtful observations. Astronomical J 2:161-163.
– reference: Slob W. 2002. Dose-response modeling of continuous endpoints. Toxicol Sci 66:298-312.
– reference: Kirsch-Volders M, Aardema M, Elhajouji A. 2000. Concepts of threshold in mutagenesis and carcinogenesis. Mutat Res 464:3-11.
– reference: Cribari-Neto F, Zeileis A. 2010. Beta regression in R. J Stat Software 34:1-24.
– reference: Manjanatha MG, Shelton SD, Bishop M, Shaddock JG, Dobrovolsky VN, Heflich RH, Webb PJ, Blankenship LR, Beland FA, Greenlees KJ, et al. 2004. Analysis of mutations and bone marrow micronuclei in Big Blue® rats fed leucomalachite green. Mutat Res 547:5-18.
– reference: Trentin GA, Moody J, Heddle JA. 1998. Effect of maternal folate levels on somatic mutation frequency in the developing colon. Mutat Res 405:81-87.
– reference: Dobrovolsky VN, Miura D, Heflich RH, Dertinger SD. 2010. The in vivo Pig-a gene mutation assay, a potential tool for regulatory safety assessment. Environ Mol Mutagen 51:825-835.
– reference: Kimoto T, Suzuki K, Kobayashi Xm, Dobrovolsky VN, Heflich RH, Miura D, Kasahara Y. 2011. Manifestation of Pig-a mutant bone marrow erythroids and peripheral blood erythrocytes in mice treated with N-ethyl-N-nitrosourea: Direct sequencing of Pig-a cDNA from bone marrow cells negative for GPI-anchored protein expression. Mutat Res 723:36-42.
– reference: Robinson DR, Goodall K, Albertini RJ, O'Neill JP, Finette B, Sala-Trepat M, Moustacchi E, Tates AD, Beare DM, Green MHL, et al. 1994. An analysis of the in vivo hprt mutant frequency in circulating T-lymphocytes in the normal human population: a comparison of four datasets. Mutat Res 313:227-247.
– reference: Cosentino L, Heddle JA. 1999. A comparison of the effects of diverse mutagens at the LacZ transgene and Dlb-1 locus in vivo. Mutagenesis 14:113-119.
– reference: Heddle JA, Dean S, Nohmi T, Boerrigter M, Casciano D, Douglas GR, Glickman BW, Gorelick NJ, Mirsalis JC, Martus H-J, et al. 2000. In vivo transgenic mutation assays. Environ Mol Mutagen 35:253-259.
– reference: Nohmi T, Katoh M, Suzuki H, Matsui M, Tamada M, Watanabe M, Suzuki M, Horiya N, Ueda O, Shibuya T, et al. 1996. A new transgenic mouse mutagenesis test system using Spi- and 6-thioguanine selections. Environ Mol Mutagen 28:465-470.
– reference: Gocke E, Wall M. 2009. In vivo genotoxicity of EMS: Statistical assessment of the dose response curves. Toxicol Lett 190:298-302.
– reference: European Food Safety Authority (EFSA). 2009. Guidance of the scientific committee on a request from EFSA on the use of the benchmark dose approach in risk assessment. EFSA J 1150:1-72.
– reference: Dobo KL, Fiedler RD, Gunther WC, Thiffeault CJ, Cammerer Z, Coffing SL, Shutsky T, Schuler M. 2011. Defining EMS and ENU dose-response relationships using the Pig-a mutation assay in rats. Mutat Res 725:13-21.
– reference: Lambert IB, Singer TM, Boucher SE, Douglas GR. 2005. Detailed review of transgenic rodent mutation assays. Mutat Res 590:1-280.
– reference: Takahashi M, Takeda J, Hirose S, Hyman R, Inoue N, Miyata T, Ueda E, Kitani T, Medof ME, Kinoshita T. 1993. Deficient biosynthesis of N-acetylglucosaminyl-phospatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor biosynthesis, in cell lines established from patients with Paroxysmal Nocturnal Hemoglobinuria. J Exp Med 177:517-521.
– reference: van Sittert NJ, Boogaard PJ, Natarajan AT, Tates AD, Ehrenberg LG, Tornqvist MA. 2000. Formation of DNA adducts and induction of mutagenic effects in rats following 4 weeks inhalation exposure to ethylene oxide as a basis for cancer risk assessment. Mutat Res 447:27-48.
– reference: Lutz WK, Lutz RW. 2009. Statistical model to estimate threshold dose and its confidence limits for the analysis of sublinear dose-response relationships, exemplified for mutagenicity data. Mutat Res 678:118-122.
– reference: Bhalli JA, Pearce MG, Dobrovolsky VN, Heflich RH. 2011. Manifestation and persistence of Pig-a mutant red blood cells in C57BL/6 mice following single and split doses of N-ethyl-N-nitrosourea. Environ Mol Mutagen 52:766-773.
– reference: Müller L, Gocke E. 2009. Considerations regarding a permitted daily exposure calculation for ethyl methanesulfonate. Toxicol Lett 190:330-332.
– year: 2011
– year: 2009
– volume: 90
  start-page: 10681
  year: 1993
  end-page: 10685
  article-title: Comparison of somatic mutation in a transgenic versus host locus
  publication-title: Proc Natl Acad Sci USA
– volume: 678
  start-page: 118
  year: 2009
  end-page: 122
  article-title: Statistical model to estimate threshold dose and its confidence limits for the analysis of sublinear dose‐response relationships, exemplified for mutagenicity data
  publication-title: Mutat Res
– volume: 34
  start-page: 1
  year: 1999
  end-page: 8
  article-title: Spectra of mutations in ethylnitrosourea‐treated and untreated transgenic mice
  publication-title: Environ Mol Mutagen
– volume: 678
  start-page: 95
  year: 2009
  end-page: 100
  article-title: Non‐linear dose‐response of DNA‐reactive genotoxins: Recommendations for data analysis
  publication-title: Mutat Res
– volume: 10
  start-page: 365
  year: 1970
  end-page: 377
  article-title: Fate and metabolism of some mutagenic alkylating agents in the mouse. I. Ethyl methanesulfonate and methyl methanesulfonate at sublethal dose in hybrid males
  publication-title: Mutat Res
– volume: 49
  start-page: 256
  year: 2008
  end-page: 264
  article-title: In vivo mutation assay based on the endogenous locus
  publication-title: Environ Mol Mutagen
– volume: 313
  start-page: 227
  year: 1994
  end-page: 247
  article-title: An analysis of the in vivo mutant frequency in circulating T‐lymphocytes in the normal human population: a comparison of four datasets
  publication-title: Mutat Res
– volume: 35
  start-page: 253
  year: 2000
  end-page: 259
  article-title: In vivo transgenic mutation assays
  publication-title: Environ Mol Mutagen
– volume: 447
  start-page: 27
  year: 2000
  end-page: 48
  article-title: Formation of DNA adducts and induction of mutagenic effects in rats following 4 weeks inhalation exposure to ethylene oxide as a basis for cancer risk assessment
  publication-title: Mutat Res
– volume: 151
  start-page: 29
  year: 2004
  end-page: 41
  article-title: Carcinogenicity categorization of chemicals‐new aspects to be considered in a European perspective
  publication-title: Toxicol Lett
– volume: 119
  start-page: 346
  year: 2011
  end-page: 358
  article-title: ‐Methylpurine DNA glycosylase plays a pivotal role in the threshold response of ethylmethansulfonate‐induced chromosome damage
  publication-title: Toxicol Sci
– volume: 190
  start-page: 298
  year: 2009
  end-page: 302
  article-title: In vivo genotoxicity of EMS: Statistical assessment of the dose response curves
  publication-title: Toxicol Lett
– volume: 49
  start-page: 614
  year: 2008a
  end-page: 621
  article-title: Development of an in vivo gene mutation assay using the endogenous gene: I. Flow cytometric detection of CD59‐negative peripheral red blood cells and CD48‐negative spleen T‐cells from the rat
  publication-title: Environ Mol Mutagen
– volume: 31
  start-page: 105
  year: 2009
  end-page: 118
  article-title: Spontaneous and induced and Spi mutant frequencies in delta transgenic rodents
  publication-title: Gene Environ
– volume: 51
  start-page: 825
  year: 2010
  end-page: 835
  article-title: The in vivo gene mutation assay, a potential tool for regulatory safety assessment
  publication-title: Environ Mol Mutagen
– volume: 52
  start-page: 766
  year: 2011
  end-page: 773
  article-title: Manifestation and persistence of mutant red blood cells in C57BL/6 mice following single and split doses of ‐ethyl‐ ‐nitrosourea
  publication-title: Environ Mol Mutagen
– volume: 49
  start-page: 622
  year: 2008b
  end-page: 630
  article-title: Development of an in vivo gene mutation assay using the endogenous gene: II. Selection of mutant rat spleen T‐cells with proaerolysin and sequencing cDNA from the mutants
  publication-title: Environ Mol Mutagen
– volume: 73
  start-page: 787
  year: 2010
  end-page: 806
  article-title: Bayesian analysis of a rat formaldehyde DNA‐protein cross‐link model
  publication-title: J Toxicol Environ Health A
– volume: 54
  start-page: 8
  year: 2013
  end-page: 18
  article-title: Quantitative approaches for assessing dose‐response relationships in gentic toxicology studies
  publication-title: Environ Mol Mugagen
– volume: 177
  start-page: 517
  year: 1993
  end-page: 521
  article-title: Deficient biosynthesis of ‐acetylglucosaminyl‐phospatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor biosynthesis, in cell lines established from patients with Paroxysmal Nocturnal Hemoglobinuria
  publication-title: J Exp Med
– volume: 7)
  start-page: 1
  year: 1987
  end-page: 440
– volume: 96
  start-page: 5209
  year: 1999
  end-page: 5214
  article-title: Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals
  publication-title: Proc Natl Acad Sci USA
– volume: 20
  start-page: 315
  year: 2001
  end-page: 325
  article-title: Low doses and thresholds in genotoxicity: From theories to experiments
  publication-title: J Exp Clin Cancer Res
– volume: 28
  start-page: 465
  year: 1996
  end-page: 470
  article-title: A new transgenic mouse mutagenesis test system using Spi and 6‐thioguanine selections
  publication-title: Environ Mol Mutagen
– volume: 52
  start-page: 784
  year: 2011
  end-page: 794
  article-title: Monitoring humans for somatic mutation in the endogenous gene using red blood cells
  publication-title: Environ Mol Mutagen
– volume: 1150
  start-page: 1
  year: 2009
  end-page: 72
  article-title: Guidance of the scientific committee on a request from EFSA on the use of the benchmark dose approach in risk assessment
  publication-title: EFSA J
– volume: 753
  start-page: 82
  year: 2013
  end-page: 92
  article-title: Evaluating the weak micronucleus response of a genotoxic carcinogen, Aristolochic acids
  publication-title: Mutat Res
– volume: 7
  start-page: 212
  year: 1990
  end-page: 218
  article-title: The use of transgenic mice for short‐term, in vivo mutagenicity testing
  publication-title: Genet Anal Tech Appl (GATA)
– volume: 190
  start-page: 254
  year: 2009b
  end-page: 265
  article-title: Literature review on the genotoxicity, reproductive toxicity, and carcinogenicity of ethyl methanesulfonate
  publication-title: Toxicol Lett
– volume: 34
  start-page: 1
  year: 2010
  end-page: 24
  article-title: Beta regression in R
  publication-title: J Stat Software
– volume: 1044
  start-page: 97
  year: 2013
  end-page: 119
– volume: 20
  start-page: 1
  year: 2003
  end-page: 12
– volume: 86
  start-page: 8620
  year: 1989
  end-page: 8624
  article-title: Site‐specific mutagenesis by ‐alkylguanines located in the chromosomes of mammalian cells: Influence of the mammalian ‐alkylguanine‐DNA alkyltransferase
  publication-title: Proc Natl Acad Sci USA
– start-page: 391
  year: 1996
  end-page: 410
– volume: 657
  start-page: 122
  year: 2008
  end-page: 126
  article-title: Erythrocyte‐based gene mutation assay: Demonstration of cross‐species potential
  publication-title: Mutat Res
– volume: 14
  start-page: 113
  year: 1999
  end-page: 119
  article-title: A comparison of the effects of diverse mutagens at the transgene and locus
  publication-title: Mutagenesis
– volume: 52
  start-page: 419
  year: 2011
  end-page: 423
  article-title: Analysis of mutations in the gene of spleen T‐cells from ‐ethyl‐ ‐nitrosourea‐treated Fisher 344 rats
  publication-title: Environ Mol Mutagen
– volume: 134
  start-page: 113
  year: 1984
  end-page: 142
  article-title: A review of the genetic effects of EMS
  publication-title: Mutat Res
– year: 2012
– volume: 678
  start-page: 101
  year: 2009
  end-page: 107
  article-title: studies in the mouse to define a threshold for the genotoxicity of EMS and ENU
  publication-title: Mutat Res
– volume: 190
  start-page: 287
  year: 2009a
  end-page: 297
  article-title: MNT and Muta™Mouse studies to define the dose response relations of the genotoxicity of EMS and ENU
  publication-title: Toxicol Lett
– volume: 547
  start-page: 5
  year: 2004
  end-page: 18
  article-title: Analysis of mutations and bone marrow micronuclei in Big Blue® rats fed leucomalachite green
  publication-title: Mutat Res
– volume: 405
  start-page: 81
  year: 1998
  end-page: 87
  article-title: Effect of maternal folate levels on somatic mutation frequency in the developing colon
  publication-title: Mutat Res
– volume: 190
  start-page: 271
  year: 2009
  end-page: 285
  article-title: General 4‐week toxicity study with EMS in the rat
  publication-title: Toxicol Lett
– volume: 464
  start-page: 3
  year: 2000
  end-page: 11
  article-title: Concepts of threshold in mutagenesis and carcinogenesis
  publication-title: Mutat Res
– volume: 725
  start-page: 13
  year: 2011
  end-page: 21
  article-title: Defining EMS and ENU dose‐response relationships using the mutation assay in rats
  publication-title: Mutat Res
– volume: 590
  start-page: 1
  year: 2005
  end-page: 280
  article-title: Detailed review of transgenic rodent mutation assays
  publication-title: Mutat Res
– year: 2006
– volume: 132
  start-page: 87
  year: 2013
  end-page: 95
  article-title: Influence of DNA repair on nonlinear dose‐responses for mutation
  publication-title: Toxicol Sci
– volume: 190
  start-page: 333
  year: 2009
  end-page: 339
  article-title: The Viracept‐EMS case: Impact and outlook
  publication-title: Toxicol Lett
– volume: 66
  start-page: 298
  year: 2002
  end-page: 312
  article-title: Dose‐response modeling of continuous endpoints
  publication-title: Toxicol Sci
– volume: 455
  start-page: 191
  year: 2000
  end-page: 215
  article-title: Recent advances in the protocols of transgenic mouse mutation assays
  publication-title: Mutat Res
– volume: 86
  start-page: 7971
  year: 1989
  end-page: 7975
  article-title: Efficient rescue of integrated shuttle vectors from transgenic mice: A model for studying mutations
  publication-title: Proc Natl Acad Sci USA
– volume: 723
  start-page: 36
  year: 2011
  end-page: 42
  article-title: Manifestation of mutant bone marrow erythroids and peripheral blood erythrocytes in mice treated with ‐ethyl‐ ‐nitrosourea: Direct sequencing of cDNA from bone marrow cells negative for GPI‐anchored protein expression
  publication-title: Mutat Res
– volume: 190
  start-page: 330
  year: 2009
  end-page: 332
  article-title: Considerations regarding a permitted daily exposure calculation for ethyl methanesulfonate
  publication-title: Toxicol Lett
– volume: 540
  start-page: 141
  year: 2003
  end-page: 151
  article-title: transgenic mutation assays
  publication-title: Mutat Res
– volume: 223
  start-page: 373
  year: 1989
  end-page: 375
  article-title: Micronucleus test with ethyl methanesulfonate administered by intraperitoneal injection and oral gavage
  publication-title: Mutat Res
– volume: 2
  start-page: 161
  year: 1852
  end-page: 163
  article-title: Criterion for the rejection of doubtful observations
  publication-title: Astronomical J
– ident: e_1_2_7_22_1
  doi: 10.1073/pnas.86.20.7971
– ident: e_1_2_7_19_1
  doi: 10.1016/j.toxlet.2009.03.021
– ident: e_1_2_7_51_1
  doi: 10.1084/jem.177.2.517
– ident: e_1_2_7_36_1
  doi: 10.3123/jemsge.31.105
– ident: e_1_2_7_48_1
– ident: e_1_2_7_12_1
  doi: 10.1002/em.20667
– ident: e_1_2_7_25_1
– volume: 20
  start-page: 315
  year: 2001
  ident: e_1_2_7_61_1
  article-title: Low doses and thresholds in genotoxicity: From theories to experiments
  publication-title: J Exp Clin Cancer Res
– ident: e_1_2_7_50_1
  doi: 10.1093/toxsci/66.2.298
– ident: e_1_2_7_37_1
  doi: 10.1002/(SICI)1098-2280(1999)34:1<1::AID-EM1>3.0.CO;2-P
– ident: e_1_2_7_60_1
  doi: 10.1093/toxsci/kfq341
– ident: e_1_2_7_42_1
  doi: 10.1002/(SICI)1098-2280(1996)28:4<465::AID-EM24>3.0.CO;2-C
– ident: e_1_2_7_54_1
  doi: 10.1016/j.mrgentox.2003.07.004
– ident: e_1_2_7_59_1
  doi: 10.1080/15287391003689234
– ident: e_1_2_7_40_1
  doi: 10.1002/em.20654
– ident: e_1_2_7_14_1
  doi: 10.1073/pnas.86.22.8620
– ident: e_1_2_7_44_1
  doi: 10.1086/100259
– volume: 1150
  start-page: 1
  year: 2009
  ident: e_1_2_7_13_1
  article-title: Guidance of the scientific committee on a request from EFSA on the use of the benchmark dose approach in risk assessment
  publication-title: EFSA J
– ident: e_1_2_7_16_1
– ident: e_1_2_7_5_1
  doi: 10.1016/j.toxlet.2004.04.004
– ident: e_1_2_7_57_1
  doi: 10.1007/978-1-4899-0301-3_29
– ident: e_1_2_7_2_1
  doi: 10.1073/pnas.96.9.5209
– ident: e_1_2_7_32_1
  doi: 10.1016/j.mrrev.2005.04.002
– ident: e_1_2_7_38_1
  doi: 10.1002/em.20414
– ident: e_1_2_7_10_1
  doi: 10.1016/j.mrgentox.2011.06.005
– ident: e_1_2_7_20_1
  doi: 10.1016/j.toxlet.2009.03.016
– ident: e_1_2_7_46_1
  doi: 10.1016/j.mrgentox.2008.08.011
– ident: e_1_2_7_11_1
  doi: 10.1002/em.20627
– ident: e_1_2_7_8_1
  doi: 10.18637/jss.v034.i02
– volume: 134
  start-page: 113
  year: 1984
  ident: e_1_2_7_49_1
  article-title: A review of the genetic effects of EMS
  publication-title: Mutat Res
  doi: 10.1016/0165-1110(84)90007-1
– ident: e_1_2_7_39_1
  doi: 10.1002/em.20413
– ident: e_1_2_7_7_1
  doi: 10.1093/mutage/14.1.113
– ident: e_1_2_7_58_1
  doi: 10.1016/j.toxlet.2009.03.027
– ident: e_1_2_7_55_1
  doi: 10.1016/S0027-5107(98)00147-X
– ident: e_1_2_7_28_1
  doi: 10.1016/j.mrgentox.2011.03.016
– ident: e_1_2_7_43_1
  doi: 10.1016/S0027-5107(00)00077-4
– ident: e_1_2_7_3_1
  doi: 10.1002/em.20682
– ident: e_1_2_7_53_1
  doi: 10.1093/toxsci/kfs341
– ident: e_1_2_7_6_1
  doi: 10.1002/em.20379
– ident: e_1_2_7_31_1
  doi: 10.1016/0165-1218(89)90089-X
– ident: e_1_2_7_56_1
  doi: 10.1016/S0027-5107(99)00208-0
– ident: e_1_2_7_47_1
  doi: 10.1016/0165-1161(94)90053-1
– ident: e_1_2_7_35_1
  doi: 10.1007/978-1-62703-529-3_5
– ident: e_1_2_7_30_1
  doi: 10.1016/0735-0651(90)90003-X
– ident: e_1_2_7_4_1
  doi: 10.1016/j.mrgentox.2013.03.002
– ident: e_1_2_7_33_1
  doi: 10.1016/j.mrgentox.2009.05.010
– ident: e_1_2_7_17_1
  doi: 10.1016/j.mrgentox.2009.04.005
– ident: e_1_2_7_45_1
  doi: 10.1016/j.toxlet.2009.04.031
– ident: e_1_2_7_9_1
  doi: 10.1016/0027-5107(70)90049-7
– ident: e_1_2_7_41_1
  doi: 10.1016/j.toxlet.2009.03.015
– ident: e_1_2_7_34_1
  doi: 10.1016/j.mrfmmm.2003.11.009
– ident: e_1_2_7_24_1
  doi: 10.1002/(SICI)1098-2280(2000)35:3<253::AID-EM11>3.0.CO;2-J
– ident: e_1_2_7_52_1
  doi: 10.1073/pnas.90.22.10681
– ident: e_1_2_7_29_1
  doi: 10.1016/S1383-5718(99)00161-8
– ident: e_1_2_7_18_1
  doi: 10.1016/j.toxlet.2009.03.008
– ident: e_1_2_7_21_1
  doi: 10.1002/em.21727
– ident: e_1_2_7_26_1
– ident: e_1_2_7_23_1
– ident: e_1_2_7_27_1
  doi: 10.1016/j.mrgentox.2009.05.009
– ident: e_1_2_7_15_1
SSID ssj0011492
Score 2.2188911
Snippet The assumption that mutagens have linear dose–responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA‐reactive mutagen and...
The assumption that mutagens have linear dose-responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA-reactive mutagen and...
SourceID proquest
pubmed
crossref
wiley
istex
SourceType Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 385
SubjectTerms Animals
benchmark dose
bilinear model
Bone marrow
DNA Damage - drug effects
DNA Damage - genetics
dose-response
Dose-Response Relationship, Drug
Escherichia coli Proteins - physiology
Ethyl Methanesulfonate - toxicity
gene mutation
Genotoxicity
gpt
Hypoxanthine Phosphoribosyltransferase - genetics
Lac Operon - genetics
Male
Membrane Proteins - genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
micronucleus
Micronucleus Tests
Mutagenicity
Mutagens
Mutagens - toxicity
Mutation
Mutation - genetics
Mutation Rate
NOGEL
Pentosyltransferases - physiology
Pig-a
Reticulocytes - drug effects
Spleen - drug effects
threshold
Title Quantitative dose-response analysis of ethyl methanesulfonate genotoxicity in adult gpt-delta transgenic mice
URI https://api.istex.fr/ark:/67375/WNG-GT9XR41C-R/fulltext.pdf
https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fem.21854
https://www.ncbi.nlm.nih.gov/pubmed/24535894
https://www.proquest.com/docview/1531535297
https://www.proquest.com/docview/1532950564
https://www.proquest.com/docview/1551624981
Volume 55
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1ba9RAFB6kIvii1utqKyOIPmWbmcwtj1J6QWjBpcUFH4bJzESW7mbrbgLVp_4EwX_YX-KZyUUqVcSnEHLC3M7ly-TMdxB6zQ1JFXNlYkuWJeDwZGKynIMup9yGA2qqDAecj47F4Sl7P-XTLqsynIVp-SGGDbdgGdFfBwM3xXrnF2moX4whPPFABRpStQIemgzMUYDyYz3kFMJxIkROe97ZlO70L16LRLfDpF7cBDOvo9YYdvbvo099h9tsk7NxUxdj--03Lsf_G9EDdK9Do_hdqz6b6JavHqI7bX3Kr4_Qlw-NqeIpNPCJ2C3X_uryx6rNqvXYdHwmeFliD-s9x6EctQHf2czLsCnvcWCArZcXMwtYH88qHNk-8Ofz-uryu_Pz2uA6xEoQm1m8AJ_1GJ3u753sHiZdjYbEMiVYonKeFhkvpQPTdpQaKw0plKFSFCJk3FhJuCMmh5tSlZI5xkuhCibSLDMuy56gjWpZ-WcIW0cKoqShXlImfaakI14wYQQFnFPkI_S2Xy9tOwLzUEdjrlvqZar9QscJHKFXg-R5S9pxg8ybuOSDgFmdhSQ3yfXH4wN9cJJPJ4zs6skIbfU6oTv7XmuIEyQQ4-QS2hoeg2WG3y0w0csmytA8AEz2NxlOBHwBKzJCT1t9GzpEGbSg8tDTqDV_HIreO4rX5_8q-ALdBdzH2oy3LbRRrxq_DdiqLl5GK_oJIXEf7A
linkProvider Wiley-Blackwell
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V3LbtQwFLWqVgg2vB8DBYzEY5Vp7PiVBQvU15R2RmI0Fd0ZJ3HQqPMoMxnRsuonIPEZ_Apf0S_h2nmgooLYdMEqinKlOPbxvcfO9bkIPeeGhIpleZDmLArA4cnARDEHLIc8dQfUVO4OOHd7orPP3h7wgyX0vT4LU-pDNBtubmZ4f-0muNuQXvulGmrHbYhPnFUZlbv25DOs1-avdzZgcF9QurU5WO8EVUmBIGVKsEDFPEwinssMkJhRalJpSKIMlSIRLkEklYRnxMRwk6tcsozxXKiEiTCKTOZ2P8Hfr7gC4k6of6PfaFXBusJXYA6BAARCxLRWug3pWt3Sc7FvxQ3j8UXE9jxP9oFu6wb6UXdRmd9y2F4USTv98pt65H_ShzfR9Ypw4zflDLmFluzkNrpSluA8uYM-vVuYiT9oB24fZ9O5PTv9NisThy02lWQLnubYAqRH2FXcNhAeFqPc_Xew2IncFtPjYQrLGTycYC9ogj8eFWenXzM7KgwuHB0As2GKx-CW76L9S_nee2h5Mp3YBwinGUmIkoZaSZm0kZIZsYIJIyhQuSRuoVc1QHRaabS7UiEjXapLU23H2g9YCz1rLI9KXZILbF56jDUGZnbo8vgk1-9723p7EB_0GVnX_RZarUGoKxc21xAKidP-iSW8q3kMzsf9UYKOni68DY0dh2Z_s-FEwCJfkRa6XwK8aRBl8AYVu5Z6mP7xU_Rm118f_qvhU3S1M-ju6b2d3u4jdA1oLisT_FbRcjFb2MdAJYvkiZ_CGH24bLz_BEe6ev4
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V3JbhQxELWiRCAu7MtAACOxnHrSdnvrAweUySQhZARRIubWuNtuNMpszPSIhFM-AYm_4Ff4i3wJZfeCggLikgOnltUleXuuKtvlVwg95ZqEipk8yHIWBaDwZKCjmAOWQ565B2oqdw-cd3ti64C97vP-Evpev4Up-SGaAze3Mry-dgt8avK1X6ShdtQG88RZFVC5Y48_w3Zt_nK7A3P7jNLuxv76VlBlFAgypgQLVMzDNOK5NABEQ6nOpCap0lSKVLj4kEwSboiOoZCrXDLDeC5UykQYRdq4w09Q9ytQjF2aiM5eQ1UF2wqfgDkE-x8IEdOa6Daka3VLz5i-FTeLR-f5tWfdZG_nutfQj3qEyvCWw_aiSNvZl9_II_-PIbyOrlbuNn5Vro8baMmOb6JLZQLO41vo07uFHvtndqD0sZnM7enJt1kZNmyxrghb8CTHFgA9xC7ftgbjsBjm7tbBYkdxW0yOBhlsZvBgjD2dCf44LU5Pvho7LDQunDMAYoMMj0Ap30YHF9LfO2h5PBnbewhnhqRESU2tpEzaSElDrGBCCwqOXBq30IsaH0lWMbS7RCHDpOSWpokdJX7CWuhJIzktWUnOkXnuIdYI6Nmhi-KTPHnf20w29-P-HiPryV4LrdYYTCoFNk_AEBLH_BNLqKv5DarH3SfBQE8WXobGzoNmf5PhRMAWX5EWulviu2kQZVCDil1LPUr_2JVkY9d_7_-r4GN0-W2nm7zZ7u08QFfAx2VldN8qWi5mC_sQ_MgifeQXMEYfLhruPwFEt3mt
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Quantitative+dose%E2%80%93response+analysis+of+ethyl+methanesulfonate+genotoxicity+in+adult+gpt%E2%80%90delta+transgenic+mice&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.au=Cao%2C+Xuefei&rft.au=Mittelstaedt%2C+Roberta+A.&rft.au=Pearce%2C+Mason+G.&rft.au=Allen%2C+Bruce+C.&rft.date=2014-06-01&rft.issn=0893-6692&rft.eissn=1098-2280&rft.volume=55&rft.issue=5&rft.spage=385&rft.epage=399&rft_id=info:doi/10.1002%2Fem.21854&rft.externalDBID=10.1002%252Fem.21854&rft.externalDocID=EM21854
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0893-6692&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0893-6692&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0893-6692&client=summon