Studies on the cellular toxicity of polychlorinated biphenyls (PCBs). I. Effect of PCBs on microsomal enzymes and on synthesis and turnover of microsomal and cytoplasmic lipids of rat liver- a morphological and biochemical study.
The acute effects of the PCB (polychlorinated biphenyls) mixture (Aroclor 1254) on microsomal enzymes and on synthesis and turnover of microsomal and cytoplasmic lipids of rat liver were investigated. Six daily i.p. injections of 25 and 50 mg PCB/kg body weight resulted in increased liver weight and liver to body weight ratios. When compared to controls PCB treatment resulted in a six-fold increase in amount of cytochrome P-450. Activities of NADPH-cytochrome c reductase, ethylmorphine demethylase and inosine diphosphatase were increased whereas glucose-6-phosphatase values were decreased by PCB exposure. Analysis of liver homogenate and microsomal fraction revealed an increase in lipid in PCB-exposed animals. Phospholipids, cholesterol and triglyceride were significantly increased after PCB exposure; however, the greatest percentage increase was seen in the triglyceride pool. The finding of an increase in microsomal triglyceride to phospholipid ratios with exposure to PCB is suggestive of an increase in membrane-enclosed lipid (liposomes). Studies with labelled glycerol indicated that the PCB-induced fatty liver resulted from increased half life but not increased synthesis of liver lipid moieties. The rate of incorporation of leucine into microsomal membrane and albumin was somewhat enhanced in rats exposed to PCB indicative of increased protein synthesis. Morphological studies showed increased occurrence of lipid material, both in cytoplasmic droplets and within rough and smooth-surfaced endoplasmic reticulum. Proliferation of smooth endoplasmic reticulum and flattened Golgi cisternae with no secretion granules containing lipoprotein particles characterized the liver from animals exposed for 6 days. The increase in lipid within membranes of the endoplasmic reticulum together with the flattened Golgi lacking typical secretory vesicles indicates a defect in transport of lipoproteins from the endoplasmic reticulum to the Golgi apparatus and may be the cause of the PCB-induced fatty liver.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009696:Nucleic Acids / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D014280:Triglycerides / Q000378:metabolism*
D001140:Aroclors; D009696:Nucleic Acids; D010743:Phospholipids; D011506:Proteins; D014280:Triglycerides; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls