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Comparative induction of gene mutations and chromosome damage by 1-methoxy-1,3,5-cycloheptatriene (MCHT), 2. Results using L5178Y mouse lymphoma cells to detect both gene and chromosome damage; validation with ionizing radiation, methyl methanesulphonate, ethyl methanesulphonate and benzo[a]pyrene.

Abstract
A variation of the mouse lymphoma (L5178Y TK+/(-)-3.7.2c) assay has been developed using a microtiter cloning technique instead of the standard agar method. The cell line has been used to detect both gene mutations (at the Na+/K+ ATPase and thymidine kinase loci) and chromosome damage (micronucleus induction) in the same experiment. The system was validated using gamma-irradiation (a known clastogen), 2 direct-acting mutagens, ethyl and methyl methanesulphonate and an indirect-acting mutagen, benzo[a]pyrene. Using the assay, 1-methoxy-1,3,5-cycloheptatriene was shown to be a clastogenic mutagen in the presence of S9, since a clear dose-dependent increase in micronuclei was observed, mainly small colony thymidine kinase mutants were observed, and no ouabain-resistant mutants were induced, a profile very similar to gamma-irradiation. The results suggest that metabolic activation potential explains the results in the accompanying paper (Asquith et al., 1990). The implications for mutagenicity testing are discussed.
AuthorsJ Cole, M C Diot, F N Richmond, B A Bridges
JournalMutation research (Mutat Res) Vol. 230 Issue 1 Pg. 81-91 (May 1990) ISSN: 0027-5107 [Print] Netherlands
PMID2342500 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Cycloheptanes
  • Mutagens
  • 1-methoxy-1,3,5-cycloheptatriene
  • Benzo(a)pyrene
  • Ethyl Methanesulfonate
  • Methyl Methanesulfonate
Topics
  • Animals
  • Benzo(a)pyrene (toxicity)
  • Chromosome Aberrations
  • Chromosomes (drug effects, radiation effects)
  • Cloning, Molecular
  • Cycloheptanes (toxicity)
  • DNA Damage
  • Ethyl Methanesulfonate (toxicity)
  • Genes (drug effects)
  • Lymphoma
  • Methyl Methanesulfonate (toxicity)
  • Mice
  • Micronucleus Tests
  • Mutagens
  • Mutation
  • Tumor Cells, Cultured

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