Plasmid pKM101 muc(-)- and muc(+)-mediated anthracycline mutagenicity and cytotoxicity in Salmonella typhimurium.
Muc (mutagenesis: UV: chemical) genes of plasmid pKM101, along with the chromosomal gene recA are known to be important constituents for full expression of inducible error-prone DNA repair in Salmonella typhimurium. This study investigates the affects of muc+ pKM101 and three of its derivatives bearing muc- point mutations (pGW1, pGW16, and pGW21) on spontaneous as well as anthracycline-induced back mutation to histidine independence. Different base-substitution and frameshift his- tester strains of S typhimurium were treated with the anthracyclines daunomycin, Adriamycin, carminomycin, and 4-demethoxy-doxorubicin. In many cases the muc- plasmids did mediate dose-dependent anthracycline mutagenicity as measured by His+ reversion. In many of the his- strains, the presence of muc+ pKM101 or muc- plasmids also resulted in a concomitant elevation of spontaneous reversion patterns over those seen with the plasmid-free parent strains. As a result, the sensitivity of most strains to anthracycline mutagenicity (based on His+ revertants/spontaneous background/microgram anthracycline) was not enhanced by muc+ pKM101 or its muc- mutant derivatives. In contrast, the low incidence of spontaneous His+ reversion in strains of the hisD3052 series, along with the inherently greater sensitivities of these strains to anthracycline-induced reversion, demonstrate most dramatically the mutagenesis-enhancing effects of muc+ pKM101 and muc- plasmids. In these and other cases in which muc- plasmid effects on enhancement of strain sensitivity to mutagenesis or cytotoxicity are observed, the overall spectrum of enhancement is the following, in decreasing order: pKM101 greater than pGW16 greater than pGW1 greater than no plasmid approximately equal to pGW21. Possible correlations are drawn between muc- plasmid effects on anthracycline-induced mutagenesis and cytotoxicity.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic; D004926:Escherichia coli / Q000187:drug effects; D005798:Genes, Bacterial; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D009279:Naphthacenes / Q000494:pharmacology; D010957:Plasmids; D012486:Salmonella typhimurium / Q000187:drug effects; D013045:Species Specificity; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D009153:Mutagens; D009279:Naphthacenes