New Functions for Niacin Imply a Role in Cancer Prevention

Abstract

A new focus for studies of the relationship between niacin and cancer has evolved from the discovery that the principal form of this vitamin, NAD, is consumed as a substrate in ADP-ribose transfer reactions. Four unique classes of ADP-ribosyltransferases that are responsible for the turnover of NAD have been identified, although their functions are yet poorly understood. One of these, poly(ADP-ribose) polymerase, generates polymers of ADP-ribose by the successive transfer of ADP-ribose groups from NAD. This enzyme is activated by DNA strand breaks and functions in repair of DNA. The biochemical characterization of poly(ADP-ribose) polymerase has shown that the K_m of the enzyme for NAD is in the same range as the intracellular concentration of NAD in tissues. The significance of this finding is increased by the observations that: nutritional deprivation of nicotinamide in model in vitro systems readily results in decreased intracellular NAD, and limiting niacin intake in humans to levels found in the lowest quartile in the US population also results in a decrease of up to 70% of intracellular NAD [Fu, et al., J. Nutr 119: 1949 (1989)].