Concentrations and Rates of Synthesis of Nicotinamide-adenine-dinucleotide Phosphate in Precancerous Livers and Hepatomas induced by Azo-dye Feeding

Abstract

IN recent years considerable interest has been aroused in the possible role of the rate of synthesis and the concentration and oxidation state of NADP as regulatory factors in metabolism. In view of the well-known fact that tumours have a low level of NADP, and especially of NADPH₂^1–3, it seemed of importance to measure the rate of synthesis of NADP and its oxidation-reduction state in both the precancerous phase and in fully developed hepatomas, as a preliminary step in elucidating the role of this compound in tumour metabolism. Although the rate of synthesis of NAD has been measured in some tumours (see Morton⁴) there is a paucity of data on the rates of synthesis of NADP (see Reid⁵). To this end we have measured the concentration of NADP in the livers of rats after relatively short periods of feeding with carcinogens (between 14 and 30 days with either 4-dimethylamino-3′-methylazobenzene (3′ MeDAB) or 4-dimethylamino-4′-fluoroazobenzeno (4′ F DAB)) as well as in the hepatomas developed after long periods of treatment with azo-dyes. In addition we have measured the acid-labile NADP recently described by Burch, Lowry and Von Dippe⁶. Although the physiological significance of this form of NADP is not entirely clear it seemed worth investigating since it was possible that this more labile, and perhaps ‘bound’ form, could be an important component in tumour tissue, particularly in view of the finding that the glucose-6-phosphate dehydrogenase activity of liver tumours is high^3,7,8.