Comparison of mutagenicity and inducibility of DNA single-strand breaks and chromosome aberrations in cultured mouse cells by potent mutagens.
Induction of 8-azaguanine-resistant mutation, DNA single-strand breaks, and chromosome aberrations by treatment with ethyl methanesulfonate (EMS), N-methyl-N'nitro-N-nitrosoguanidine (MNNG), nitrogen mustard hydrochloride (HN2), or 4-nitroquinoline 1-oxide (4-NQO) was compared under similar experimental conditions using cultured FM3A cells from a C3H mouse mammary carcinoma. All the chemicals induced 8-azaguanine-resistant mutations and chromosome aberrations in a dose-dependent manner; a good correlation between the two activities was demonstrated. An alkaline sucrose gradient method demonstrated that DNA single-strand breaks were induced only in a high dose range by 1- and 24-hr treatment with the chemicals. One exception was that a 1-hr treatment with HN2 produced an anomalous sedimentation pattern. These data suggest that caution is necessary for the interpretation of results obtained by the alkaline sucrose gradient analysis, and that examination of mutagenicity and chromosome aberrations is more feasible as screening procedures for potential mutagens than analysis of DNA single-strand breaks.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000818:Animals; D001375:Azaguanine / Q000494:pharmacology; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D002869:Chromosome Aberrations; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004351:Drug Resistance; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D008466:Mechlorethamine / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation / Q000187:drug effects*
D004277:DNA, Single-Stranded; D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D008466:Mechlorethamine; D015112:4-Nitroquinoline-1-oxide; D005020:Ethyl Methanesulfonate; D001375:Azaguanine