The bleomycin amplification assay in V79 cells predicts frameshift mutagenicity of intercalative agents.
We have recently reported on the use of a cell-based bleomycin amplification assay for the detection of DNA intercalating agents. In order to further validate this assay, two series of proprietary compounds were evaluated for frameshift mutagenesis in the Ames bacterial reversion system and for bleomycin amplification in the Chinese hamster V79 micronucleus system. It is shown that 10 of 11 frameshift-positive compounds were bleomycin amplifiers. These studies indicate that positive frameshift mutagenicity findings are consistent with expectations from the results of the bleomycin amplification assay, providing additional validation of the amplification assay for the detection of DNA intercalating agents. The studies also demonstrate that intercalation is necessary but not sufficient for frameshift mutagenesis since bleomycin amplifiers lacking frameshift mutagenic activity were also identified.
Snyder
R D
RD
Abbott Laboratories, D-468, AP13A, 100 Abbott Park Road, Abbott Park, IL 60064, USA. ronald.d.snyder@duontpharma.com
Diehl
M S
MS
D000818:Animals; D001761:Bleomycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003571:Cytochalasin B / Q000494:pharmacology; D016368:Frameshift Mutation / Q000187:drug effects*; D007364:Intercalating Agents / Q000494:pharmacology; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D015203:Reproducibility of Results; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D007364:Intercalating Agents; D009153:Mutagens; D001761:Bleomycin; D003571:Cytochalasin B