ON THE ROLE OF NAD IN INITIATION OF THE D EATH OR TRANSFORMATION OF THE CELLS WITH DAMAGED DNA

We consider the death of cells with damaged DNA as a consequence of a sharp fall in NAD concentration as a result of their incapability to c ompensate the use of NAD for the biosynthesis of poly(ADP-ribose) by i ts a resynthesis out of nicotinamide produced during this process. We discuss the following causes of the low rate of NAD resynthesis out of nicotinamide high rate of its removal as N-methylnicotinamide charact eristic for the cells of certain types; low activity of deamidation of nicotinamide the use of ammonia created during deamidation of nicotin amide for the biosynthesis of the nucleotide predecessors; inhibition of one or both ways of resynthesis NAD out of nicotinamide by an agent damaging the DNA structure. The resistance of the cells to an action of the agents damaging the DNA structure is ensured by induction of th e enzymes using the nicotinamide without preliminary deamidation and l owering of the nicotinamide methylation intensity. The latter brings a bout automatically enhancement of the TTP biosynthesis and proliferati on of the cells. The starting point of a cell transformation, where th e control over the rate of their division, is the violation of the pri ncipal way of NAD biosynthesis, lowering of nicotinamide methylation l evel and, accordingly enhancement of the TTP biosynthesis.