Heterogeneity of cytochrome P-450s induced by polychlorinated biphenyls. [Aroclor 1254]
The polychlorinated biphenyl mixture, Aroclor 1254, is a powerful inducer of both cytochromes P-450 and P-448 exhibiting the catalytic properties of both cytochromes in the liver. Addition of Aroclor 1254 to hepatic microsomes produces a type I difference spectrum. When administered to rats, the hemeprotein induced by Aroclor 1254 displayed spectral properties which are a combination of the spectral properties of the two cytochromes. The catalytic properties of the induced hemeproteins are a combination of the catalytic properties of cytochrome P-450 induced by phenobarbital and of cytochrome P-448 induced by 3-methylcholanthrene in rats. The biphenyl mixture markedly enhanced the cytochrome P-450-associated enzymes, including the ethylmorphine and benzphetamine N-demethylases and the hexobarbital oxidative pathway. Similarly, the cytochrome P-448 enzymic activities, including the hydroxylation of benzo(a)pyrene and of zoxazolamine were greatly enhanced. Aroclor 1254 also increased cytochrome b/sub 5/ and NADPH-cytochrome c reductase activity of liver microsomes. Enhancement of benzo(a)pyrene hydroxylase activity occurred in nonhepatic tissues, including lung, kidney, adrenals, intestine, and testis. Acute exposure of rats to Aroclor 1254 resulted in a small but significant induction of delta-aminolevulinic acid synthetase and inhibition of delta-aminolevulinic acid dehydratase but no significant accumulation of porphyrins in the liver. These results clearly demonstrate that the polychlorinated biphenyl mixture, Aroclor 1254, possesses the inducing properties of the two main classes of microsomal enzyme inducers, namely phenobarbital and 3-methylcholanthrene.
- Research Organization:
- Rockefeller Univ., New York
- OSTI ID:
- 5140424
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 252:18
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CHLORINATED AROMATIC HYDROCARBONS
BIOLOGICAL EFFECTS
CYTOCHROMES
BIOCHEMICAL REACTION KINETICS
ACUTE EXPOSURE
AROMATICS
BENZOPYRENE
CATALYSIS
CHOLANTHRENE
DRUGS
ENZYME INHIBITORS
HEALTH HAZARDS
LIVER
METABOLISM
MICROSOMES
ORGANIC CHLORINE COMPOUNDS
RATS
ANIMALS
BODY
CELL CONSTITUENTS
CONDENSED AROMATICS
DIGESTIVE SYSTEM
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
HAZARDS
HYDROCARBONS
KINETICS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANOIDS
ORGANS
PIGMENTS
REACTION KINETICS
RODENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)