Use of the Miniscreen assay to screen novel compounds for bacterial mutagenicity in the pharmacentical industry

Abstract

In vitro assays for mutagenicity are an important feature of pre-clinical testing and form part of the current regulatory testing conducted early in drug development. They can also play a part in compound selection since mutagenic compounds can be eliminated from a range of potential candidates. Bacterial tests are particularly useful in this area because they generate results quickly, though their use may be limited because they can require up to 4 g of material. A scaled-down version of the Ames test has been developed which requires only approximately 20 mg of material. Initial experiences with this assay using a range of known mutagens and novel compounds have shown that the Miniscreen has similar sensitivity to the Ames test. The major exception is for those mutagens preferentially detected with strains TA1537 and TA1535, which, because of their low spontaneous counts, are not employed in the Miniscreen.

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

“…A greater than twofold increase in the number of revertant colonies over the vehicle control was indicative of a mutagenic response [Burke et al, 1996].…”

“…Approximately 140 mg of test material is required for a standard screening assay with single petri plates without analytical assay. Because many pharmaceutical candidate compounds are available in only very small quantities early in development, a scaled-down version of the Ames test (Miniscreen) was developed that allows the Ames test to be carried out using approximately 20 mg of test compound [Burke et al, 1996]. This Miniscreen Ames test utilizes 25-well Repli dishes, which require manual counting of the colonies.…”

Genetic Toxicity:In VitroApproaches for Medicinal Chemists

“…Many laboratories use streamlined versions of the regulatory Ames test in which a reduced set of strains is used, and a smaller number of colonies may be counted to estimate mutation rate [39]. While practical for candidate selection, this is still not suitable for profiling assessments.…”

Genetic Toxicity: In Vitro Approaches for Hit and Lead Profiling

“…Many laboratories use cutdown versions of the regulatory Salmonella reverse mutation assay in which a reduced set of strains is used, and a smaller number of colonies may be counted to estimate mutation rate [20]. Whilst practical for candidate selection this is still not suitable for profiling factories.…”