Peroxisome-associated enzymes and serum lipids in tumour-bearing rats treated with peroxisome-proliferating agents

Abstract

Xenobiotic induction of liver peroxisomes is associated with hypolipidemia. To test the involvement of the peroxisome proliferation with the hypolipidemia, male rats were inoculated in the groin with five different tumors: an aflatoxin-induced hepatoma, a lasiocarpine-induced hepatoma, an actinomycin-D-induced mesothelioma, a lasiocarpine-induced squamous cell carcinoma, and a methylnitrosourea-induced fibrosarcoma. After the tumours reached a suitable size, the rats were fed diets containing the peroxisome-proliferating hypolipidemic agents tibric acid (2-chloro-5-[3,5-dimethylpiperidinosulfonyl] benzoic acid) or Wy-14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid) for 2 weeks. Liver and tumor tissues were then assayed for the peroxisome-associated enzymes, catalase and carnitine acetyltransferase, and correlated with serum levels of triglyceride and cholesterol. The presence of the tumors caused a predictable decrease in liver catalase and a slight elevation of liver carnitine acetyltransferase. Serum cholesterol was elevated slightly, while serum triglyceride levels were elevated, unchanged, or decreased in the tumor-bearing rats maintained on control diet. Inclusion of the xenobiotics in the diet caused increases in liver weight, catalase, and carnitine acetyltransferase. Serum triglycerides were decreased in the three groups which were not already decreased, but a decrease in serum cholesterol was only found in one group after only one of the treatments. The latter finding demonstrates that peroxisomal enzyme induction can be dissociated from the decrease in serum cholesterol. The data were further evaluated by testing for correlations between the changes in these components, comparing changes within groups and between groups. These correlations indicate an inverse biological association between liver catalase and serum cholesterol and between liver carnitine acetyltransferase and serum triglyceride. The latter correlation was inverse only for comparisons between groups, suggesting that carnitine acetyltransferase activity is associated with serum triglycerides only during the perturbational state.