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Carcinogenesis

7-Methoxy-2-nitronaphtho[2,1-b]furan (R7000)-induced mutation spectrum in the lacI gene of Escherichia coli: influence of SOS mutagenesis.


PMID 9006087

Abstract

The mutagenic specificity of 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000), a very potent genotoxic 2-nitrofuran, was investigated in the lacI gene of E.coli. To analyze the influence of SOS-mutagenesis on R7000-induced mutations, 86 and 84 LacI- mutants were respectively isolated from umuC+ and umuC strains. Treatment of bacteria with increasing concentrations of R7000, affected 2-4 times more the survival rate in the umuC context, as compared to umuC+. 80% of all mutations occurred primarily at G:C base pairs and were substitution events and single-base frameshifts (-1) in the same proportions. The six possible substitution events were observed in both strains. In the umuC+ context, they were dominated by G:C-->T:A transversions. 38% of substitutions at G:C base pairs occurred in the consensus sequence 5'TGGCG3' or 5'TGGC3' where the G was mutated. When umuC was deficient G:C-->C:G transversions were mainly observed. The proportions of substitution mutations were very similar to those that have been reported for apurinic (AP) sites, suggesting strongly that one mechanism for R7000-induced mutations is the formation of intermediate abasic sites that serve as a substrate for error-prone repair. Single frameshift events consisted essentially of deletions of one (G:C) base pair in runs of contiguous G or C residues. Frameshift frequency increased with the length of the reiterated sequence, suggesting a strand-slippage process. Other mutational classes were recovered to a lower extent, including double-base frameshifts and large deletions. In addition, 10% of the mutants presented two proximate mutations. Comparison of the mutations induced by R7000 in the umuC+/umuC backgrounds suggests an influence of the umuC product on strand specificity of R7000-induced mutations, particularly in the case of frameshift events.

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