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Publications
  • Publisher:
    Oxford Journals
  • Publication Date:
    Jul 2015
  • Reference:
    Mutagenesis, 2015
  • DOI:
    10.1093/mutage/gev047
  • PMID:
  • Publication Type:
    Paper
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Using in vitro structural alerts for chromosome damage to predict in vivo activity and direct future testing

Canipa S; Cayley A; Drewe WC; Hamada S; Hirose A; Honma M; Morita T; Williams RV;

While the in vivo genotoxicity of a compound may not always correlate well with its activity in in vitro test systems, for certain compound classes a good overlap may exist between the two endpoints. The difficulty, however, lies in establishing the cases where this relationship holds true and selecting the most appropriate protocol to highlight any potential in vivo hazard. With this in mind, a project was initiated in which existing structural alerts for in vitro chromosome damage in the expert system Derek Nexus were assessed for their relevance to in vivo activity by assessing their predictivity against an in vivo chromosome damage data set. An expert assessment was then made of selected alerts. Information regarding the findings from specific in vivo tests was added to the alert along with any significant correlations between activity and test protocol or mechanism. A total of 32 in vitro alerts were updated using this method resulting in a significant improvement in the coverage of in vivochromosome damage in Derek Nexus against a data set compiled by the mammalian mutagenicity study group of Japan. The detailed information relating to in vivo activity and protocol added to the alerts in combination with the mechanistic information provided will prove useful in directing the further testing of compounds of interest.

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