Chlorinated hydrocarbon-induced peroxisomal enzyme activity in relation to species and organ carcinogenicity.
Trichloroethylene (TCE), perchloroethylene (PER), and pentachloroethane (PENT) are widely used industrial chemicals that cause an increased incidence of hepatocellular carcinoma in mice and a very low incidence of renal tubular adenocarcinoma in rats. A recent study (C. R. Elcombe, M. S. Rose, and I.S. Pratt (1985), Toxicol. Appl. Pharmacol. 79, 365-376) suggested that the species difference in the hepatocarcinogenicity of TCE seen between rats and mice was due to a species difference in peroxisomal proliferation and cell proliferation. The purpose of the present investigation was to understand better the association of peroxisome proliferation in the species-specific hepatocarcinogenicity, and nephrocarcinogenicity of TCE, PER, and PENT. TCE (1000 mg/kg body wt), PER (1000 mg/kg body wt), PENT (150 mg/kg body/wt), the metabolite trichloroacetic acid (TCA; 500 mg/kg body wt) or the potent peroxisome proliferating agent Wy-14,643 (WY; 50 mg/kg body wt) was administered by gavage to male F-344 rats and B6C3F1 mice for 10 days. Cyanide-insensitive palmitoyl CoA oxidation activity (PCO) was used to measure the peroxisome proliferation response. Of the chlorinated hydrocarbons, TCE and PER elevated PCO activity in mouse liver whereas only TCE elevated rat liver and kidney PCO. All agents increased PCO activity in the kidneys of mice. None of the chlorinated hydrocarbons induced a PCO response stronger than WY. These results support an association between peroxisome proliferation and hepatic tumors in mice following TCE and PER, but not PENT, administration and suggest that chlorinated hydrocarbon-induced peroxisome proliferation does not correlate with species-specific renal carcinogenicity.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity; D010088:Oxidoreductases / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity
D002273:Carcinogens; D006843:Hydrocarbons, Chlorinated; D010088:Oxidoreductases; C028427:palmitoyl CoA oxidase