Journal Article

7-Methoxy-2-nitronaphtho(2, l-b)furan (R7000)-induced mutation spectrum in the <i>lacI</i> gene of <i>Escherichia coli</i>: influence of SOS mutagenesis

Eliette Touati, Evelyne Krin, Philippe Quillardet and Maurice Hofnung

in Carcinogenesis

Volume 17, issue 12, pages 2543-2550
Published in print December 1996 | ISSN: 0143-3334
Published online December 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.12.2543
7-Methoxy-2-nitronaphtho(2, l-b)furan (R7000)-induced mutation
                    spectrum in the lacI gene of Escherichia coli:
                    influence of SOS mutagenesis

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The mutagenic specificity of 7-methoxy-2-nitronaphtho(2, l-b)furan (R7000), a very potent genotoxie 2-nitrofuran, was investigated in the lacl gene of E.coli. To analyze the influence of SOS-mutagenesis on R7000-induced mutations, 86 and 84 Lacl-mutants were respectively isolated from umuC+ and umuC strains. Treatment of bacteria with increasing concentrations of R 7000, 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 speciticity of R7000-induced mutations, particularly in the case of frameshift events.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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