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    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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    Publication date
    2020-03
    Author
    Habas, Khaled S.A.
    Brinkworth, Martin H.
    Anderson, Diana
    Keyword
    Male germ cell
    Phase specificity
    Supporting somatic cells
    DNA damage
    Apoptosis
    STAPUT gravity sedimentation
    Peer-Reviewed
    Yes
    
    Metadata
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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.
    URI
    http://hdl.handle.net/10454/17753
    Version
    No full-text in the repository
    Citation
    Habas K, Brinkworth MH and Anderson D (2020) A male germ cell assay and supporting somatic cells: its application for the detection of phase specificity of genotoxins in vitro. Journal of Toxicology and Environmental Health, Part B. 23(3): 91-106.
    Link to publisher’s version
    https://doi.org/10.1080/10937404.2020.1724577
    Type
    Abstract
    Collections
    Life Sciences Publications

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