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Fumaric acid enhances DNA synthesis of rat hepatocytes by counteracting the toxicities of mitomycin C and aflatoxin B1.

The effect of fumaric acid was examined on DNA synthesis in hepatocytes or hepatoma cells from rats treated with toxic agents. Male Donryu rats were injected with mitomycin C or aflatoxin B1, singly or in combination with fumaric acid. After a specified period, hepatocytes were isolated from the liver by the collagenase perfusion method and placed in culture, and their activities for DNA synthesis were measured. The iv injection of rats with mitomycin C (0.5 mg/kg) reduced the semiconservative DNA synthesis of the hepatocytes, but simultaneous dosing of fumaric acid (40 mg/kg) enhanced the recovery of the DNA synthesis. The DNA synthesis of hepatoma cells, a 3'-methyl-4-(dimethylamino)azobenzene-induced transplantable cell line growing in the abdominal ascites of rats, was also reduced by the iv injection of mitomycin C but, in contrast to that of the hepatocytes, was little influenced by the simultaneous dosing of fumaric acid. The ip injection of fumaric acid also reduced the toxicity of aflatoxin B1 (0.25 mg/kg, ip), preventing the reduction of DNA synthesis as well as the occurrence of nuclear degenerative changes in the aflatoxin B1-exposed hepatocytes.