Direct comparison of the Ames microplate format (MPF) test in liquid medium with the standard Ames pre-incubation assay on agar plates by use of equivocal to weakly positive test compounds

Abstract

The Ames microplate format (MPF™) test, which uses liquid media and in 384-well microplates with a readout based on a colour-change, has been used for over 10 years at several major pharmaceutical companies for screening the genotoxic potential of early drug candidates when compound supply is minimal. Meanwhile, Xenometrix has adapted this screen from the two-strain Ames II test for use with five tester strains, in compliance with OECD Guideline 471. A set of 15 equivocal to weakly positive chemicals selected from the National Toxicology Program (NTP) database was tested simultaneously in the Ames microplate format (MPF) and the standard Ames pre-incubation method on agar plates. Such a direct comparison of the two test methods with the same overnight culture(s), chemicals and S9-mix preparation should exclude external variability factors. Thirteen of the 15 chemicals showed concordant results in both tests despite the choice of chemicals that showed varying inter- and even intra-laboratory results in the NTP studies. These results indicate that the Ames MPF™ assay is a reliable predictive tool that can be used like the regular Ames test to evaluate compounds for mutagenicity.