INDUCTION EFFECTS OF POLYCHLORINATED-BIPHENYLS, POLYCYCLIC AROMATIC-HYDROCARBONS AND OTHER WIDESPREAD AROMATIC ENVIRONMENTAL-POLLUTANTS ON MICROSOMAL MONOOXYGENASE ACTIVITIES IN CHICK-EMBRYO LIVER

Cytochrome P450-dependent 7-ethoxyresorufin O-deethylase (EROD), 7-pen toxyresorufin O-dealkylase (PROD) and 7-ethoxycoumarin O-deethylase (E COD) activities in 14-day-old chick embryo livers were determined 24 h after pretreatment with selected widespread aromatic environmental co ntaminants, including polychlorinated biphenyls (PCBs), polycyclic aro matic hydrocarbons (PAHs), hexachlorobenzene, and dialkylesters of pht halic acid, and compared with the inducing potencies of 2,3,7,8-tetrac hlorodibenzo-p-dioxin (TCDD) and the coplanar and mono-o-chlorinated P CBs. The effects of other model inducers, i.e. phenobarbital and pyraz ole, were also examined. Specificity of EROD induction was estimated w ith regard to contaminants frequently present in environmental samples and dose-response curves for EROD induction were determined. A strong induction (comparable with that by mono-o-chlorinated biphenyl treatm ent) by dibenzo[a,h]anthracene, benzo[k]fluoranthene or benzo Cbl fluo ranthene was found, but the maximal level of EROD activity inducible b y TCDD was not achieved, partly due to the high toxicity of the tested PAHs. 3-Methylcholanthrene showed moderate inducing potencies, benz[a ]anthracene, benzo[a]pyrene, chrysene and 2,2',3,4,4',5'-hexachlorobip henyl appeared to be weak inducers. Other PAHs and PCBs tested, as wel l as hexachlorobenzene, dialkyl phthalates, phenobarbital and pyrazole had no marked effects on the EROD level. ECOD activities were increas ed non-specifically by TCDD, 3-methylcholanthrene: hexachlorobenzene a nd phenobarbital. A significant enhancement of PROD activity by TCDD a nd related inducers was observed, while phenobarbital induced the PROD activity only weakly; SDS-PAGE analysis showed that the chicken pheno barbital-inducible cytochromes P4502H with apparent molecular weights 50 kDa were not markedly induced by the TCDD- or 3-methylcholanthrene treatments. Inhibition of EROD and PROD by 9-hydroxyellipticine, a spe cific inhibitor of rat hepatic cytochrome P4501A1, revealed that PROD induction by TCDD and other P4501A-inducers was probably a result of a broader substrate specificity of chick embryo P4501A. Measurement of EROD activities in chick embryo liver is highly sensitive, specific an d suitable for the determination of TCDD-type toxicity of new drugs, a grochemicals, and industrial pollutants.