IMPLICATION OF CYTOCHROME-P-450 1A ISOFORMS AND THE AH RECEPTOR IN THE GENOTOXICITY OF COAL-TAR FUME CONDENSATE AND BITUMEN FUME CONDENSATES

During the hot application of bitumen- or coal-tar-containing material s: fumes are emitted that contain polycyclic aromatic compounds. Altho ugh workers' exposure to these fumes is low, it might lead to health p roblems. No study has reported the metabolic pathways involved in the genotoxicity of coal tar or bitumen fume condensates (CTFC, BFCs). We have therefore studied the DNA adducts formed by incubation of CTFC or BFCs with liver microsomes from several type of mice and with yeast m icrosomes expressing individual human CYP enzymes. Our results demonst rates that: (1) the aryl hydrocarbon receptor (AHR) plays an important role in the biotransformation of BFCs and to a lesser extent of CTFC; (2) for CTFC, both cytochrome P450 (CYP) IA isoforms are involved in the formation of genotoxic compounds, and the reactive metabolites for med via CYP 1Al, are substrates for epoxide hydrolase (mEH); (3) for B FCs, the genotoxicity is partially dependent upon CYP 1Al and the reac tive metabolites are not substrates for mEH; (4) CYP 1A isoforms are n ot exclusively responsible for the genotoxicity of the CTFC and BFCs a s other CYPs and also enzymes of the [AH] gene battery, may play an im portant role. (C) 1998 Elsevier Science B.V. All rights reserved.