title: 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.
authors.affiliation: MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton, Great Britain.
authors.forename: J
authors.initials: J
authors.lastname: Cole
authors.forename: M C
authors.initials: MC
authors.lastname: Diot
authors.forename: F N
authors.initials: FN
authors.lastname: Richmond
authors.forename: B A
authors.initials: BA
authors.lastname: Bridges
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects / Q000528:radiation effects; D003001:Cloning, Molecular; D003508:Cycloheptanes / Q000633:toxicity*; D004249:DNA Damage; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D005796:Genes / Q000187:drug effects; D008223:Lymphoma; D008741:Methyl Methanesulfonate / Q000633:toxicity; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens; D009154:Mutation; D014407:Tumor Cells, Cultured
chemical_list: D003508:Cycloheptanes; D009153:Mutagens; C064256:1-methoxy-1,3,5-cycloheptatriene; D001564:Benzo(a)pyrene; D005020:Ethyl Methanesulfonate; D008741:Methyl Methanesulfonate