A male germ cell assay and supporting somatic cells: its application for the detection of phase specificity of genotoxins in vitro
Male germ stem cells are responsible for transmission of genetic information to the next generation. Some chemicals exert a negative impact on male germ cells, either directly, or indirectly affecting them through their action on somatic cells. Ultimately, these effects might inhibit fertility, and...
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Published in | Journal of toxicology and environmental health. Part B, Critical reviews Vol. 23; no. 3; pp. 91 - 106 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
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England
Taylor & Francis
02.04.2020
Taylor & Francis Ltd |
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Abstract | Male germ stem cells are responsible for transmission of genetic information to the next generation. Some chemicals exert a negative impact on male germ cells, either directly, or indirectly affecting them through their action on somatic cells. Ultimately, these effects might inhibit fertility, and may exhibit negative consequences on future offspring. Genotoxic anticancer agents may interact with DNA in germ cells potentially leading to a heritable germline mutation. Experimental information in support of this theory has not always been reproducible and suitable in vivo studies remain limited. Thus, alternative male germ cell tests, which are now able to detect phase specificity of such agents, might be used by regulatory agencies to help evaluate the potential risk of mutation. However, there is an urgent need for such approaches for identification of male reproductive genotoxins since this area has until recently been dependent on in vivo studies. Many factors drive alternative approaches, including the (1) commitment to the principles of the 3R's (Replacement, Reduction, and Refinement), (2) time-consuming nature and high cost of animal experiments, and (3) new opportunities presented by new molecular analytical assays. There is as yet currently no apparent appropriate model of full mammalian spermatogenesis in vitro, under the REACH initiative, where new tests introduced to assess genotoxicity and mutagenicity need to avoid unnecessary testing on animals. Accordingly, a battery of tests used in conjunction with the high throughput STAPUT gravity sedimentation was recently developed for purification of male germ cells to investigate genotoxicity for phase specificity in germ cells. This system might be valuable for the examination of phases previously only available in mammals with large-scale studies of germ cell genotoxicity in vivo. The aim of this review was to focus on this alternative approach and its applications as well as on chemicals of known in vivo phase specificities used during this test system development. |
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AbstractList | Male germ stem cells are responsible for transmission of genetic information to the next generation. Some chemicals exert a negative impact on male germ cells, either directly, or indirectly affecting them through their action on somatic cells. Ultimately, these effects might inhibit fertility, and may exhibit negative consequences on future offspring. Genotoxic anticancer agents may interact with DNA in germ cells potentially leading to a heritable germline mutation. Experimental information in support of this theory has not always been reproducible and suitable
studies remain limited. Thus, alternative male germ cell tests, which are now able to detect phase specificity of such agents, might be used by regulatory agencies to help evaluate the potential risk of mutation. However, there is an urgent need for such approaches for identification of male reproductive genotoxins since this area has until recently been dependent on
studies. Many factors drive alternative approaches, including the (1) commitment to the principles of the 3R's (Replacement, Reduction, and Refinement), (2) time-consuming nature and high cost of animal experiments, and (3) new opportunities presented by new molecular analytical assays. There is as yet currently no apparent appropriate model of full mammalian spermatogenesis
, under the REACH initiative, where new tests introduced to assess genotoxicity and mutagenicity need to avoid unnecessary testing on animals. Accordingly, a battery of tests used in conjunction with the high throughput STAPUT gravity sedimentation was recently developed for purification of male germ cells to investigate genotoxicity for phase specificity in germ cells. This system might be valuable for the examination of phases previously only available in mammals with large-scale studies of germ cell genotoxicity
. The aim of this review was to focus on this alternative approach and its applications as well as on chemicals of known
phase specificities used during this test system development. Male germ stem cells are responsible for transmission of genetic information to the next generation. Some chemicals exert a negative impact on male germ cells, either directly, or indirectly affecting them through their action on somatic cells. Ultimately, these effects might inhibit fertility, and may exhibit negative consequences on future offspring. Genotoxic anticancer agents may interact with DNA in germ cells potentially leading to a heritable germline mutation. Experimental information in support of this theory has not always been reproducible and suitable in vivo studies remain limited. Thus, alternative male germ cell tests, which are now able to detect phase specificity of such agents, might be used by regulatory agencies to help evaluate the potential risk of mutation. However, there is an urgent need for such approaches for identification of male reproductive genotoxins since this area has until recently been dependent on in vivo studies. Many factors drive alternative approaches, including the (1) commitment to the principles of the 3R's (Replacement, Reduction, and Refinement), (2) time-consuming nature and high cost of animal experiments, and (3) new opportunities presented by new molecular analytical assays. There is as yet currently no apparent appropriate model of full mammalian spermatogenesis in vitro, under the REACH initiative, where new tests introduced to assess genotoxicity and mutagenicity need to avoid unnecessary testing on animals. Accordingly, a battery of tests used in conjunction with the high throughput STAPUT gravity sedimentation was recently developed for purification of male germ cells to investigate genotoxicity for phase specificity in germ cells. This system might be valuable for the examination of phases previously only available in mammals with large-scale studies of germ cell genotoxicity in vivo. The aim of this review was to focus on this alternative approach and its applications as well as on chemicals of known in vivo phase specificities used during this test system development. |
Author | Brinkworth, Martin H. Habas, Khaled Anderson, Diana |
Author_xml | – sequence: 1 givenname: Khaled surname: Habas fullname: Habas, Khaled email: K.habas@bradford.ac.uk organization: Faculty of Life Sciences, University of Bradford – sequence: 2 givenname: Martin H. surname: Brinkworth fullname: Brinkworth, Martin H. organization: Faculty of Life Sciences, University of Bradford – sequence: 3 givenname: Diana surname: Anderson fullname: Anderson, Diana email: d.anderson1@bradford.ac.uk organization: Faculty of Life Sciences, University of Bradford |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32046612$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1080_03602532_2021_1917597 crossref_primary_10_1080_15287394_2021_1992323 |
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Snippet | Male germ stem cells are responsible for transmission of genetic information to the next generation. Some chemicals exert a negative impact on male germ cells,... |
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SubjectTerms | Animal research Anticancer properties Antitumor agents Apoptosis Deoxyribonucleic acid DNA DNA damage Fertility Genotoxicity Germ cells In vivo methods and tests Male germ cell Mammals Mutagenicity Mutation Offspring phase specificity Purification Regulatory agencies Sedimentation Somatic cells Spermatogenesis STAPUT gravity sedimentation Stem cell transplantation Stem cells supporting somatic cells |
Title | A male germ cell assay and supporting somatic cells: its application for the detection of phase specificity of genotoxins in vitro |
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