Alteration of Hepatic DNA Synthesis in Rats Treated with N-Nitrosodimethylamine during Early Stages of Copper Deficiency

The main aim of this research was to clarify that nutritional dietary copper may participate in the protective action against hepatocarcinogenesis in rats by N-nitrosodimethylamine (NDMA). The copper concentrations in serum and liver from 2 to 8 d after rats were first fed a copper deficient diet (copper, 0.6 ppm) decreased significantly compared to those of pair-fed rats (copper in a control diet, 7 ppm). The subcellular distribution of copper in the liver at 5 d after feeding of a copper deficient diet began was measured and the copper concentrations in soluble and nuclear fractions decreased at a similar rate in copper deficient rats treated with or without NDMA, compared to those of pair-fed rats. The incorporation of [3H]thymidine into rat liver DNA at 48 h after treatment with NDMA markedly increased under the experimental conditions used. By giving rats a copper deficient diet for a few days the increased incorporation of [3H]thymidine into liver DNA of rats treated with NDMA was enhanced compared to that of pair-fed rats treated with NDMA. The activity of thymidine kinase in liver of copper deficient rats treated with NDMA was also found to increase ingnificantly compared to that of pair-fed rats treated with NDMA.