Low response of DNA synthesis upon growth stimulation in LEC mutant rat

Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a chronically necrotizing hepatic injury at 4 months of age, exhibits an excess hepatic copper accumulation. DNA synthesis upon growth stimulation in LEC rat primary-cultured hepatocytes markedly decreased when compared to that of normal rat hepatocyte culture. Low response of DNA synthesis seems to be associated with nuclear disorganization induced by copper toxicity. However, LEC rat electrophoretic profile and content of each histone component responsible for DNA stability were indistinguishable from those of normal rat. These results suggest that copper-generated damage of substrates other than histones causes nuclear damage in LEC rat.