In silico model for mutagenicity (Ames test), taking into account metabolism.

Bacterial reverse mutation test is one of the most common methods used to address genotoxicity. The experimental test is designed to include a step to simulate mammalian metabolism. The most common metabolic activation system is the incubation with S9 fraction prepared from the livers of rodents. Usually, in silico models addressing this endpoint are developed on the basis of an overall call disregarding the fact that the toxic effect was observed before or after metabolic activation. Here, we present a new in silico model to predict mutagenicity as measured by activity in the bacterial reverse mutation test, bearing in mind the role of S9 activation to stimulate metabolism. We applied the software SARpy, which identifies structural alerts associated with the effect. Different rules codified by these structural alerts were found in case of positive or negative mutagenicity, observed in the presence or absence of the S9 fraction. These rules can be used to understand the role of metabolism in mutagenicity better. We also identified a possible association of the results from these models with carcinogenicity.