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 assessment of the mutagenic potential of chemicals. The assay is widely used in the pharmaceutical industry for early assessment during candidate compound selection and for regulatory drug submissions. Early in development, many candidate compounds are available in only very small quantities. The use of the standard plate incorporation bacterial reverse mutation assay for screening, using only a single petri plate per concentration, requires the use of approximately 140 mg of test compound to test up to a stock concentration of 100 mg/ml (5000 microg/plate) in five strains of bacteria. A modification of the existing Ames Miniscreen assay has been developed using six-well cell-culture dishes that requires only 21 mg of compound to test a stock concentration of up to 100 mg/ml (2000 microg/well) in three strains of bacteria. The standard plate incorporation assay and the modified Miniscreen assays conducted on proprietary compounds without and with metabolic activation have yielded a high degree of concordance in findings.