Comparison of the results of a modified miniscreen and the standard bacterial reverse mutation assays

The bacterial reverse mutation assay (Ames test) provides a rapid assessmen t of the mutagenic potential of chemicals. The assay is widely used in the pharmaceutical industry For early assessment during candidate compound sele ction and for regulatory drug submissions. Early in development, many candi date compounds are available in only very small quantities. The use of the standard plate incorporation bacteriol reverse mutation assay For screening , using only a single petri plate per concentration, requires the use of ap proximately 140 mg of test compound to test up to a stock concentration of 100 mg/ml (5000 mu g/plate) in five strains of bacteria. A modification of the existing Ames Miniscreen assay has been developed using six-well cell-c ulture dishes that requires only 21 mg of compound to test a stock concentr ation of up to 100 mg/ml (2000 mu g/well) in three strains of bacteria. The standard plate incorporation assay and the modified Miniscreen assays cond ucted on proprietary compounds without and with metabolic activation have y ielded a high degree of concordance in findings. Environ. (C) 2000 Wiley-Li ss, Inc.