The Quantitative Structure-Mutagenicity Relationship of Polycylic Aromatic Hydrocarbon Metabolites

摘要

Quantitative structure-activity relationships (QSARs) for benz[a]anthracene (BA) mutagens using 73 descriptors were searched. The mutagenicity data was obtained from Ames assays for Mycobacterium vanbaalenii, Mycobacterium gilvum and Mycobacterium flavescens strains. These data were fitted using a mutagenicity-cytotoxicity competition model which defines the mutagenic potencies of BA metabolites, and include oxides, phenols, quinones, and dihydrodiols. The QSAR equations were derived using the molecular descriptor set (charged partial surface area, spatial, thermodynamic and electronic descriptors) and semi-empirical energetic and charge descriptors. Genetic function approximation was used to reduce and fit independent variables, including linear- and quadratic-based functions. Multiple QSAR equations were generated and a separate QSAR equation was chosen and evaluated for each strain using conventional r2, F-test, and cross-validated r2. Each strain exhibited its own characteristic descriptors.