The concentration and biosynthesis of nicotinamide nucleotides in the livers of rats treated with carcinogens

Abstract

The oxidoreduction state and concentration of both NAD (nicotinamide adenine dinucleotide) and NADP (triphos-phopyridine nucleotide) as well as the maximum potential activities of NMN (N,-methylnicotinamide) adenyltransferase and NAD+kinase have been measured in the livers of rats treated for 14[long dash]28 days with 4-dimethylamino-3[image]-methylazobenzene, 4-dimethylamino-4[image]-fluoroazobenzene, [alpha]-napthyl isothiothiocyanate or ethionine and in primary hepatomas induced by 4-dimethylamino-3[image]-methylazobenzene. The total NAD and total NADP both decreased in the livers of rate treated with either azodyes or [alpha]-naphthyl isothiocyanate but not in those treated with ethionine. The activities of NMN adenyltransferase and NAD+kinase did not alter appreciably after such treatments. In the primary hepatomas the concentrations of both NAD and NADP fell drastically and the activities of NMN adenyltransferase and NAD+ kinase fell to about 50% of the control activities. No correlation could be established between the concentrations of the nucleotides and the activities of the enzymes synthesizing them. It appears, however, that a relationship exists between the NAD content of the tissue and the amount of NADP present. The results are discussed with respect to the control of NAD and NADP synthesis by ATP (adenosine triphosphate). At the concentrations of NAD normally present in the cell it is suggested that NAD may be a rate-limiting substrate in NADP synthesis.