Mutational spectrum of N-hydroxy-N-acetyl-4-aminobiphenyl at exon 3 of the HPRT gene

4-Aminobiphenyl is a human bladder carcinogen present in many environmental sources, including cigarette smoke. It can be metabolized in two steps to the mutagen N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP). In this study the mutational spectrum of N-OH-AABP-exposed human lymphoblastoid cells (TK6...

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Published inBiomarkers Vol. 6; no. 4; pp. 262 - 273
Main Authors ZAYAS-RIVERA, Beatriz, LIFANG ZHANG, GRANT, Stephen G, KEOHAVONG, Phouthone, DAY, Billy W
Format Journal Article
LanguageEnglish
Published London Informa UK Ltd 2001
Taylor & Francis
Subjects
Biological and medical sciences
Chemical mutagenesis
Hprt Aminobiphenyl Denaturant Gradient Gel Electrophoresis Mutational Spectrum
Medical sciences
Toxicology
Human
Enzyme
Metabolite
Toxicity
Preservation agent
Transferases
Glycosyltransferases
Hypoxanthine phosphoribosyltransferase
Mutagen
Metabolism
In vitro
Site of action
Exon
Biphenyl derivatives
Mutation
Pentosyltransferases
Biphenyl-4-ylamine
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Abstract 4-Aminobiphenyl is a human bladder carcinogen present in many environmental sources, including cigarette smoke. It can be metabolized in two steps to the mutagen N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP). In this study the mutational spectrum of N-OH-AABP-exposed human lymphoblastoid cells (TK6) was determined using HPRT
AbstractList 4-Aminobiphenyl is a human bladder carcinogen present in many environmental sources, including cigarette smoke. It can be metabolized in two steps to the mutagen N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP). In this study the mutational spectrum of N-OH-AABP-exposed human lymphoblastoid cells (TK6) was determined using HPRT
4-Aminobiphenyl is a human bladder carcinogen present in many environmental sources, including cigarette smoke. It can be metabolized in two steps to the mutagen N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP). In this study the mutational spectrum of N-OH-AABP-exposed human lymphoblastoid cells (TK6) was determined using HPRT as the target gene. Three large, HAT (hypoxanthine-aminopterin-thymidine)-cleaned TK6 cultures were independently treated with 20 mu M N-OH-AABP for 24h, allowed to recover for 4 days, then continuously exposed to 40 mu M 6-thioguanine to select for induced mutants. Contemporary control cultures received vehicle in place of N-OH-AABP. N- OH-AABP treatment gave an 11-fold increase in mutation frequency. Mutations were delineated in exon 3 of the HPRT gene directly from genomic DNA extracted from both treated and untreated cells using the polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE) and dideoxy sequencing. DGGE analysis showed N-OH-AABP increased both the number and type of mutations as compared with controls. The major background mutation was a G(197) arrow right A transition. The major N-OH-AABP-induced changes were G(209-211) arrow right T transversions (30%), a seven-base repeat at position 185 (17%) and an A(215) arrow right T transversion (2%). The shift in the control spectrum of a transition to that of transversions and insertions suggest that the electrophile N-OH-AABP forms bulky adducts at the same sites on exon 3 of HPRT as do many other bulky electrophiles, causes replication errors by similar mechanisms, but induces at least one potentially signature mutation.
4-Aminobiphenyl is a human bladder carcinogen present in many environmental sources, including cigarette smoke. It can be metabolized in two steps to the mutagen N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP). In this study the mutational spectrum of N-OH-AABP-exposed human lymphoblastoid cells (TK6) was determined using HPRT.
Author Beatriz Zayas-Rivera, Lifang Zhang, Stephen G. Grant, Phouthone Keohavong, Billy W. Day
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Issue 4
Keywords Human
Enzyme
Metabolite
Toxicity
Preservation agent
Transferases
Glycosyltransferases
Hypoxanthine phosphoribosyltransferase
Mutagen
Metabolism
In vitro
Site of action
Exon
Biphenyl derivatives
Mutation
Pentosyltransferases
Biphenyl-4-ylamine
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FISHER S. G. (CIT0004) 1983; 80
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Snippet 4-Aminobiphenyl is a human bladder carcinogen present in many environmental sources, including cigarette smoke. It can be metabolized in two steps to the...
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SubjectTerms Biological and medical sciences
Chemical mutagenesis
Hprt Aminobiphenyl Denaturant Gradient Gel Electrophoresis Mutational Spectrum
Medical sciences
Toxicology
Title Mutational spectrum of N-hydroxy-N-acetyl-4-aminobiphenyl at exon 3 of the HPRT gene
URI https://www.tandfonline.com/doi/abs/10.1080/13547500010017367
https://www.ncbi.nlm.nih.gov/pubmed/23889278
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