Reference

Peroxisome proliferators increase the formation of BPDE-DNA adducts in isolated rat hepatocytes

Peroxisome proliferators increase the formation of BPDE-DNA adducts in isolated rat hepatocytes. Voskoboinik, I.; Ooi, S. G.; Drew, R.; Ahokas, J. T. (Key Centre for Applied and Nutritional Toxicology, RMIT-University, GPO Box 2476V, Melbourne, Victoria 3001, Australia). Toxicology, 122(1,2), 81-91 (English) 1997 Elsevier. CODEN: TXCYAC. ISSN: 0300-483X. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) In this study the effect of peroxisome proliferators silvex and di(2-ethylhexyl) phthalate (DEHP) on the formation of (+)-anti-benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide (BPDE)-DNA adducts from a proximate mutagen and carcinogen (-)-trans-benzo[a]pyrene-7,8-dihydrodiol (BPDD) has been investigated. Rat CYP1A1 metabolizes BPDD to mutagenic BPDE, which may form DNA adducts or, alternatively, be detoxified by hydrolysis or glutathione conjugation. In this expt. the formation of BPDE-DNA adducts was significantly increased in hepatocytes isolated from all silvex treated rats and two out of four DEHP treated rats (14 day treatment). The activity of CYP1A1 was increased whereas glutathione S-transferase (GST) was reduced by the peroxisome proliferator silvex. These changes were more significant than those induced by DEHP. We have hypothesized that the formation of BPDE-DNA adducts was primarily due to the increased BPDD activation to BPDE vs. reduced detoxication of BPDE. Other hepatic changes induced by the peroxisome proliferators, e.g. peroxisome proliferation per se and increased mitotic activity of the liver could have an effect on the outcome of BPDD exposure. 60864-95-1 are also occured in this study. .