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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1991 May;82(5):503–510. doi: 10.1111/j.1349-7006.1991.tb01879.x

Different Effects of Carbon Tetrachloride on Carcinogen–induced Hepatocellular Carcinoma and Normal Liver of the Rat: Lowered Lipid Feroxidation and Accelerated Necrosis in Cancer

Nirush Lertprasertsuke 1,†, Masayuki Shinoda 1,‡, Susumu Takekoshi 1, Yutaka Tsutsumi 1, Yorihiro Yamamoto 2, Etsuo Niki 2, Keiichi Watanabe 1,✉
PMCID: PMC5918484  PMID: 1905697

Abstract

To investigate molecular responses to lipid peroxidative stimuli in neoplastic cells, lipid peroxidation was induced in liver of rats bearing 3′‐methyl‐4‐dimethylaminoazobenzene‐induced hepatocellular carcinoma by injecting a high dose of carbon tetrachloride (CCL4), a strong lipoperoxidative reagent. Normal rat livers with or without CCl4 treatment served as controls. CCL4, administration markedly provoked fatty metamorphosis, visualized by oil red O staining, in normal livers while minimal fatty changes were seen in hepatocellular carcinomas, where necrosis was often observed instead. After CCl4 treatment, the thiobarbituric acid values (representing levels of lipid peroxides in the tissue) were increased two–fold in the untreated normal liver, but were unchanged in the cancer tissue. Levels of vitamin C, an acutely reactive antioxidant, measured by high‐performance liquid chromatography were not influenced by the CCL4 injection in the cancer tissue whereas a significant decrease was evident in normal livers. The total fatty acid content, measured by gas chromatography, was significantly lower in the cancer tissue than in the normal liver while the ratio of polyunsaturated fatty acids (PUFAs) in total fatty acids was little changed. Resistance of hepatocellular cancer cells to fatty metamorphosis and their susceptibility to necrosis induced by free radicals may be due to the paucity of the target PUFAs in their cell membrane fraction, resulting in low levels of lipid peroxides. Peroxidation of PUFAs might act as a “shock absorber” against free radical‐induced toxic cell death in normal cells.

Keywords: Lipid peroxidation, Hepatocellular carcinoma, Polyunsaturated fatty acid, Vitamin C, Carbon tetrachloride

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