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Title: Mixed-function oxidase system induction and propylene hepatotoxicity.

Authors: Osimitz, T G; Conolly, R B

Published In J Toxicol Environ Health, (1985)

Abstract: Propylene is hepatotoxic to male Charles River COBS Sprague-Dawley rats pretreated with polychlorinated biphenyls (PCB: Aroclor 1254). Four-hour inhalation exposure to 50,000 ppm propylene increased liver weight/body weight ratios and elevated serum enzyme activities in PCB-pretreated animals. Hepatic microsomal cytochrome P-450 content of PCB-pretreated rats dropped profoundly during propylene exposure and remained depressed for at least 24 h. In addition, PCB-pretreated, propylene-exposed rats exhibited a decrease in the specific activity of hepatic microsomal aniline hydroxylase. However, there was no change in activities of either hepatic microsomal aminopyrine demethylase or glucose-6-phosphatase. Propylene exposure of rats pretreated with beta-naphthoflavone (BNF), phenobarbital (PB), or a mixture of BNF and PB was not hepatotoxic. However, there was, in these animals, a substantial decline in hepatic microsomal cytochrome P-450 levels 24 h after the start of propylene exposure. Hence, the propylene-dependent process resulting in hepatic cytochrome P-450 destruction is qualitatively or quantitatively different from the process that causes acute hepatotoxicity. Preexposure fasting had no effect on the hepatotoxicity resulting from a 4-h exposure of PCB-pretreated rats to 50,000 ppm propylene. Administration of SKF-525A to PCB-pretreated rats immediately prior to propylene exposure completely prevented elevations in serum enzyme activities and liver weight/body weight ratios. In vitro incubation of hepatic microsomes prepared from either BNF-, PB-, or PCB-pretreated rats with an atmosphere of 20% propylene/80% air produced in NADPH-dependent decrease in cytochrome P-450 content. These results suggest that PCB pretreatment is a prerequisite for propylene hepatotoxicity in the rat. Cytochrome P-450-dependent bioactivation of propylene is associated with this hepatotoxicity, but further studies are needed to characterize the mechanism of the PCB-propylene interaction.

PubMed ID: 2984438 Exiting the NIEHS site

MeSH Terms: Alkenes/toxicity*; Aminopyrine N-Demethylase/metabolism; Analysis of Variance; Aniline Hydroxylase/metabolism; Animals; Aroclor 1254; Aroclors/toxicity; Atmosphere Exposure Chambers; Benzoflavones/pharmacology; Cytochrome P-450 Enzyme System/analysis; Cytochrome P-450 Enzyme System/metabolism; Drug Interactions; Enzyme Induction; Glucose-6-Phosphatase/metabolism; Male; Microsomes, Liver/drug effects*; Microsomes, Liver/enzymology; Mixed Function Oxygenases/analysis; Mixed Function Oxygenases/biosynthesis*; Organ Size/drug effects; Phenobarbital/pharmacology; Proadifen/pharmacology; Rats; Rats, Inbred Strains; beta-Naphthoflavone

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