Mutagenic and cytotoxic potencies of a series of anthracycline derivatives as measured by His+ reversion, 8-azaguanine resistance and direct plating cytotoxicity tests in Salmonella typhimurium.
His+ reversion at multiple his- loci, 8-azaguanine resistance, and a previously reported direct plating cytotoxicity test were used to measure the genotoxic potencies of a series of anthracycline derivatives in Salmonella typhimurium. N-demethylated amino sugar monosaccharide anthracyclines reverted most his- tester strains and were positive with 8-azaguanine selection. Reversion of strain TA98 was the most sensitive end point for measuring the mutagenic activity of the N-demethylated anthracyclines. N,N-dimethyl amino sugar derivatives of Adriamycin and daunomycin were negative as measured by His+ reversion in tester strain TA98, but generated positive responses in tester strain TA102 that were equal to or greater than those of the demethylated parent compounds. Similarly, N,N-dimethyl amino sugar derivatives of pyrromycinone and 1-deoxypyrromycinone had no mutagenic activity as measured by His+ reversion except in tester strains TA102 and TA104. These later compounds also gave positive responses with 8-azaguanine selection. In view of these results, the importance of amino sugar dialkylation and anthracycline mechanisms of mutagenesis are discussed.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic; D001375:Azaguanine / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D009279:Naphthacenes / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D009153:Mutagens; D009279:Naphthacenes; D001375:Azaguanine