INFLUENCE OF THE UVR-DEPENDENT NUCLEOTIDE EXCISION-REPAIR ON DNA-ADDUCTS FORMATION AND MUTAGENIC SPECTRUM OF A POTENT GENOTOXIC AGENT - 7-METHOXY-2-NITRONAPHTHO[2,1-B]FURAN (R7000)

The influence of the uvr-dependent excision repair system on the letha l action, mutagenic specificity, SOS induction and DNA adducts formati on of 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000), a potent genotoxic nitrofuran, were examined in Escherichia coli. Binding measurements o f H-3-labelled R7000 to DNA indicated that R7000-DNA adducts can be re moved by excision repair soon after the action of the chemical: 50% of the DNA adducts were removed within 10 min of treatment. After 1 h of incubation the level of excision reached 70%. This result was confirm ed using the postlabelling technique. We found that R7000 yielded at l east 10 different DNA adducts. Each of the adducts detected could be r emoved by excision repair. The rates of excision appeared different fr om one to the other. In addition, using a lacZ reversion system that i s able to detect each type of base substitution mutations [1], we foun d that in uvrA bacteria deficient in excision repair, R7000 can induce 5 out of the 6 possible mutational events: GC --> TA, AT --> TA, GC - -> CG, AT --> CG and GC --> AT. The transition AT --> GC was not obser ved. Only 3 transversions: GC --> TA, AT --> TA and GC --> CG could be detected in repair proficient uvr(+) bacteria. The differences betwee n the mutagenic spectra obtained in either uvr(+) bacteria or uvrA mut ants indicate that some potentially mutagenic DNA adducts induced by R 7000 can be removed by excision repair, thus lowering the mutagenic po tency of the chemical and modifying the mutagenic spectrum detected.