Advertisement

Co-ordinator’s Report: In vivo Assays Used in the Second UKEMS Collaborative Study

  • J. Ashby

Abstract

When this study commenced it was known that the four test agents (BZD, DAT, DAB and CDA) were genotoxic in some in vitro assays. It was therefore expected that a large proportion of the additional in vitro studies conducted within the study would also prove positive. The beginning of a rationalisation for the occasionally divergent in vitro assay results for these agents is made in the Study Overview which follows this chapter. Far less certain at the start, and probably more intriguing, was how short-term rodent assays conducted in vivo would respond to these agents. It was apparent at the start of the study that an adequate representation of the rodent bone marrow cytogenetic assays would be provided, but both of the established carcinogens in the study (BZD and DAB) were already known to be only weakly clastogenic in this tissue (de Serres and Ashby, 1980). The danger therefore existed that short-term in vivo assays would be judged collectively by the performance of the bone marrow assays. This was considered inappropriate at this critical stage in the development of in vivo assays, especially as a major in vivo study organised by the IPCS was running in parallel with this one (Ashby et al., 1983). An effort was therefore made to incorporate additional rodent assays in the study, in particular, those associated with the rodent liver, bladder, foetus and urine. This grouping remained incomplete at the end of the study, but when considered within the context of the carcinogenicity bioassay data for DAT and the extensive disposition and metabolism data generated, a useful database was formed. The present chapter considers the acute rodent assay data available and how they relate to the available carcinogenic data on these four in vitro genotoxins.

Keywords

Test Agent Study Overview Rodent Liver Animal Carcinogen Mutagenic Urine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

  1. Ashby, J. (1983). The unique role of rodents in the detection of possible human mutagens and carcinogens. Mutation Res. 115: 177–213PubMedCrossRefGoogle Scholar
  2. Ashby, J., de Serres, F.J., Draper, M.H., Ishidate, jr. M., Matter, B.E. and Shelby, M. (1983). The two IPCS collaborative studies on short-term tests for genotoxicity and carcinogenicity. Mutation Res. 109: 123–126CrossRefGoogle Scholar
  3. Ashby, J., de Serres, F.J., Draper, M.H., Ishidate, jr. M., Matter, B.E. and Shelby, M. (1985). Evaluation of Short-term Tests for Carcinogens: Results of the IPCS in vitro Study. Elsevier/ North Holland. (In press)Google Scholar
  4. de Serres, F.J. and Ashby, J. (eds.) (1981). Evaluation of Short-term Tests for Carcinogens (Progress in Mutation Research Ser. Vol.1). Elsevier/ North HollandGoogle Scholar
  5. Furihata, C. Yamawaki, Y., Jin, S. Moriya, H., Kodama, K., Matsushima, T., Ishikawa, T., Takayama, S. and Nakadate, M. (1984). Induction of unscheduled DNA synthesis in rat stomach mucosa by glandular stomach carcinogens. J. Nat. Cancer Inst. 72: 1327–1333PubMedGoogle Scholar
  6. Parry J. (ed.) (1982). The UKEMS genotoxicity trial 1981. Mutation Res. 100 Resolution: GlobalGoogle Scholar
  7. Working, P.K., Butterworth, B.E. (1984). An assay to detect chemically induced DNA repair in rat spermatocytes. Environmental Mut. 6: 273–286CrossRefGoogle Scholar

Copyright information

© United Kingdom Environmental Mutagen Society 1985

Authors and Affiliations

  • J. Ashby
    • 1
  1. 1.ICI plcCentral Toxicology LaboratoryMacclesfieldUK

Personalised recommendations