Effects of excision repair and plasmid pKM101 on mutagenic and cytotoxic potencies of anthracycline derivatives in test strains of Salmonella typhimurium.
The effects of excision repair and presence of plasmid pKM101 on the mutagenicities and cytotoxicities of the anthracycline derivatives Adriamycin, daunomycin, carminomycin, and 4-demethoxydoxorubicin were examined in strains of Salmonella typhimurium. Plasmid pKM101 has been shown to mediate inducible error-prone repair in S. typhimurium. While the test compounds were shown to produce a range of mutational responses in excision repair defective (uvrB-), pKM101-bearing strains of different his- backgrounds, proficiency in excision repair generally resulted in the elimination of mutagenic responses in all such strains except those that contain the hisG428 site. In the absence of pKM101, only hisD3052 uvrB- strain TA1538 was shown to be sensitive to anthracycline mutagenicity. A suspension (preincubation) test as well as a direct plating test showed that while proficiency in either excision repair (uvr+) or plasmid pKM101 error-prone repair afforded cellular protection against anthracycline cytotoxicity, plasmid-free uvrB- strains were most sensitive to anthracycline cytotoxicity.
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D004260:DNA Repair; D004269:DNA, Bacterial / Q000378:metabolism; D006639:Histidine / Q000235:genetics; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D009279:Naphthacenes / Q000633:toxicity; D010641:Phenotype; D010957:Plasmids; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*
D000903:Antibiotics, Antineoplastic; D004269:DNA, Bacterial; D009153:Mutagens; D009279:Naphthacenes; D006639:Histidine