Toxicology 122 (1997) 81 – 91 Peroxisome proliferators increase the formation of BPDE-DNA adducts in isolated rat hepatocytes I. Voskoboinik a , S.G. Ooi b , R. Drew c , J.T. Ahokas a, * a Key Centre for Applied and Nutritional Toxicology, RMIT-Uniersity, GPO Box 2476V, Melbourne, Victoria 3001, Australia b CMS&F Enironmental Engineers, Melbourne, Victoria 3004, Australia c ICI Australia Ltd., Melbourne, Victoria 3000, Australia Received 19 November 1996; accepted 4 May 1997 Abstract Peroxisome proliferators are known to modulate the activity of xenobiotic-metabolising enzymes, including glutathione S -transferase (GST) and cytochrome P-450 (CYP). 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-epox- ide (BPDE)-DNA adducts from a proximate mutagen and carcinogen ( -)-transbenzo(a)pyrene-7,8-dihydrodiol (BPDD) has been investigated. Rat CYP1A1 metabolises BPDD to mutagenic BPDE, which may form DNA adducts or, alternatively, be detoxified by hydrolysis or glutathione conjugation. In this experiment 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 GST was reduced by the peroxisome proliferator silvex. These changes were more significant than those induced by DEHP. We have hypothesised that the formation of BPDE-DNA adducts was primarily due to the increased BPDD activation to BPDE versus 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. © 1997 Elsevier Science Ireland Ltd. Keywords: Peroxisome proliferators; Di(2-ethylhexyl)phthalate (DEHP); Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE); Glutathione S-transferase; Cytochrome P-450 (CYP); Silvex * Corresponding author. Fax: +61 3 96636087. 0300-483X/97/$17.00 © 1997 Elsevier Science Ireland Ltd. All rights reserved. PII S0300-483X(97)00083-8