RESISTANCE TO CISPLATIN IN AN ESCHERICHIA-COLI B-R NAL(R) MUTANT

The effects of various mutations in DNA-repair processes have been rep orted to either enhance or decrease bacterial sensitivity to cis-diamm inedichloroplatinum(II) (cis-DDP). In the search for other mutations a ffecting bacterial sensitivity to this antitumor compound, we tested t he E. coli B/r BS80 mutant, which is resistant to nalidixic acid (Nal( R)). This mutation maps in the topoisomerase II gene (gyrA subunit) an d leads to cross-resistance to cis-DDP. The mechanism underlying the r esistance phenotype was only partly due to decreased DNA platination. BS80 was cross-resistant to mitomycin C and, to a lesser extent, to UV light, while it was normally sensitive to MNNG. The mechanisms involv ed in cis-DDP and mitomycin C resistance were independent of uvrA (exc ision repair) and recA (SOS repair and recombination) gene expression. In contrast, UV resistance was dependent upon recA gene expression. B oth the reversion to Nal(S) in BS80 and the transduction of Nal(R) in the parental wild type (F26) did not modify cis-DDP toxicity; in addit ion, platinated plasmids equally survived in BS80 and F26 strains. Hen ce, it is possible that selection of the Nal(R) phenotype induced othe r mutation(s) than gyrA responsible for cis-DDP, mitomycin C and UV re sistance and/or that lesions with a different toxic potential were int roduced by cis-DDP into the BS80 and F26 chromosomes.