Reduction of nicotinamide adenine dinucleotide levels by ultimate carcinogens in human lymphocytes

Abstract

The effect of several classes of DNA-damaging chemicals and closely related compounds on cellular nicotinamide adenine dinucleotide (NAD) levels was studied in freshly isolated peripheral human lymphocytes. Of the 21 compounds examined, 7 were direct DNA-damaging agents and 14 were non-DNA-damaging compounds or required metabolic activation to casue DNA damage. Rapid lowering of cellular NAD levels was caused by each of the direct DNA-damaging chemicals examined in this study including N-methyl-N'-nitr-N-nitrosoguanidine, methyl methanesulfonate, N-acetoxy-2-acetylaminofluorene, 7-bromomethylbenz(a)anthracene, and the benzo(a)pyrene derivatives, r-7,t-8-dihydroxy-9, 10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene and benzo(a)pyrene-4,5-epoxide. The indirect-acting carcinogen 2-acetylaminofluorene, 13 polycyclic aromatic hydrocarbons, and derivatives that were non-DNA-damaging did not cause lowering of NAD. The results suggest a general correlation between DNA damage and acute lowering of cellular NAD pools.