Genotoxic effects of binary mixtures of polycyclic aromatic hydrocarbons

The general goals of this project are to determine what short-term measurements best predict long-term genotoxic effects in animals exposed to multiple chemicals and to learn about the mechanisms of toxicologically significant interactions. They are initially addressing the goals by using binary mixtures of benzo[a]pyrene (BaP) and benz[a]anthracene (BaA) in cellular and cell-free systems for which the potential number of interactions is minimized. They examined the effects of BaA on the mutagenic activity of BaP as measured in the Salmonella mutagenesis assay, using relatively low and high concentrations of liver microsomes isolated from Aroclor-treated rats. The also assays genotoxicity by measuring binding of [3H-BaP] to calf thymus DNA in vitro. At both the lower and higher microsomal protein concentrations, BaA inhibited binding of [3H-BaP] to calf thymus DNA. These results are in contrast to those obtained with the mutagenesis assay of genotoxicity, in which BaA had opposite effects at the low and high protein concentrations. They are also examining the genotoxicities of BaP/BaA mixtures in the Chinese hamster ovary cell CHO/hypoxanthine-guanosyl-phosphoribosyl-transferase (CHO/HGPRT) assay, with detection of 6-thioguanine resistance