Quantification of the genotoxic effects of alkylating agents in bacterial assays.
The genotoxic effects of 11 monofunctional alkylating carcinogens in the Escherichia coli Multitest, SOS Chromotest and Salmonella assay were quantified using the 'yield versus lethal hit plot' method. In this method, the genotoxic yield-potency is defined as the integral under the yield versus lethal hit curve, whereas the genotoxic yield-efficiency is defined as the maximum yield obtained. With the series of substances tested, these two genotoxicity indices were found to be equivalent in the E. coli Multitest. The three bacterial short-term tests were compared and the following observations made: (i) the mutagenic efficiencies in the Salmonella assay and in the Multitest are correlated; (ii) the SOS-inducing efficiency in the SOS Chromotest correlates with both the SOS-inducing efficiency and the recombinogenic efficiency in the Multitest; (iii) mutagenesis and SOS induction measured by the same protocol in the Multitest are clearly distinct phenomena; (iv) when quantified with the 'yield versus lethal hit plot' method, the data from the SOS Chromotest do not correlate any more with the data from the Salmonella assay. Therefore the SOS Chromotest should be considered as a complementary rather than an alternative test to the Salmonella assay. Consequently, the Multitest appears as a relevant candidate for the basis of a battery of tests since it permits the measurement of at least two independent genotoxic effects in a single bacterial system. The method of quantification of genotoxic potencies using the 'yield versus lethal hit plot' method demonstrates the quantitative relationships existing between the data obtained using different systems measuring the same genotoxic effect and differentiates different genotoxic effects from each other.
Tenenbaum
L
L
Department of Molecular Biology, Université Libre de Bruxelles, Belgium.
Malaveille
C
C
D000477:Alkylating Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D011995:Recombination, Genetic; D013014:SOS Response, Genetics; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D013329:Structure-Activity Relationship
D000477:Alkylating Agents; D009153:Mutagens