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 lethal action, mutagenic specificity, SOS induction and DNA adducts formation of 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000), a potent genotoxic nitrofuran, were examined in Escherichia coli. Binding measurements of 3H-labelled R7000 to DNA indicated that R7000-DNA adducts can be removed 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 confirmed using the postlabelling technique. We found that R7000 yielded at least 10 different DNA adducts. Each of the adducts detected could be removed by excision repair. The rates of excision appeared different from one to the other. In addition, using a lacZ reversion system that is able to detect each type of base substitution mutations [1], we found 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 observed. Only 3 transversions: GC-->TA, AT-->TA and GC-->CG could be detected in repair proficient uvr+ bacteria. The differences between the mutagenic spectra obtained in either uvr+ bacteria or uvrA mutants indicate that some potentially mutagenic DNA adducts induced by R7000 can be removed by excision repair, thus lowering the mutagenic potency of the chemical and modifying the mutagenic spectrum detected.
Quillardet
P
P
Unité de Programmation Moléculaire et Toxicologie Génétique, CNRS Ura 1444, Institut Pasteur, Paris, France.
Touati
E
E
Hofnung
M
M
D001426:Bacterial Proteins / Q000235:genetics; D001482:Base Composition; D018736:DNA Adducts / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics*; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial / Q000235:genetics; D015394:Molecular Structure; D016296:Mutagenesis / Q000235:genetics; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology / Q000633:toxicity; D009581:Nitrofurans / Q000494:pharmacology* / Q000633:toxicity; D011485:Protein Binding; D013014:SOS Response, Genetics
D001426:Bacterial Proteins; D018736:DNA Adducts; D029968:Escherichia coli Proteins; D009153:Mutagens; D009581:Nitrofurans; C030911:2-nitro-7-methoxynaphtho(2-1b)furan; D004706:Endodeoxyribonucleases; C036385:endodeoxyribonuclease uvrABC