Effect of environmental pollutants on hepatocellular function in rats: 3-methylcholanthrene and Aroclor-1254.
Environmental pollutants, Aroclor-1254 (PCB) and 3-methylcholanthrene (MC), were employed in this study to investigate some aspects of the induction of hepatic drug metabolism in rats. PCB and MC treatments increased 7-ethoxyresorufin and 7-ethoxycoumarin O-deethylase activities related to cytochrome P-448. Cytochrome P-450 reductase activity was increased by PCB while no effect was observed by MC treatment. Pretreatment with PCB resulted in approximately 50% increase in the phospholipid content of the microsomes whereas MC caused no change. Liver microsomal cholesterol content was decreased while triglycerides were increased by PCB. The ratio between saturated and unsaturated fatty acids (saturation index) decreased in the total microsomes and phospholipids with PCB treatment, whereas MC did not alter the ratio, except that the major effect of MC was observed in the acyl derivatives of microsomal phosphatidylethanolamine. It is proposed that the uniaxial rotation and mobility of hemoproteins may be restricted by an increase in the saturation index of the membrane, while a decreased index may facilitate contact with reductases for electron transfer by enhanced membrane fluidity. The decreased saturation index after treatment with MC may play a role in carcinogenicity by triggering induction of free radicals.
D000818:Animals; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004785:Environmental Pollutants / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D014280:Triglycerides / Q000378:metabolism
D004785:Environmental Pollutants; D005227:Fatty Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011506:Proteins; D014280:Triglycerides; D020111:Chlorodiphenyl (54% Chlorine); D008748:Methylcholanthrene; D012313:RNA; D004247:DNA; D002784:Cholesterol; D006899:Mixed Function Oxygenases