MUTAGENICITY AND CARCINOGENICITY CORRELATIONS BETWEEN BACTERIA AND RODENTS

Detection of mutation in bacteria has acquired the status of an accepted procedure in genetic toxicology programs. The methods presently employed in such programs include both forward and reverse mutation-induction techniques in strains of Salmonella typhimurium and Escherichia coli. The specific strains used in these techniques have been selected over the years on the basis of their sensitivity to a broad range of chemical mutagens. In addition, it has been reported that chemical carcinogens can be presumptively identified on the basis of these assays, and bacterial testing has been generally considered the front-line test procedure for the identification of presumptive mutagenic carcinogens. An analysis of correlative studies both retrospective and cross-sectional shows a range of predictive capabilities depending on features such as chemical class, carcinogenic mechanism, and requirements for specific metabolic toxification processes. The greatest limitations associated with the use of bacteria mutation testing is the real and/or perceived issue of the test or a misinterpretation of the correlation coefficients under conditions of routine application. Concerns related to the performance (reliability, reproducibility, and predictability) and relevance of bacteria assays perpetuate controversy surrounding their application to hazard assessment. A review of several studies comparing mutation induction and tumor induction indicates that the Ames test can be useful in screening large numbers of chemicals, but the true correlation coefficient is only about 80% when compared to tumor responses in mice and rats.