EVALUATING THE ROLE OF NIACIN IN HUMAN CARCINOGENESIS

Our understanding of the role of ADP-ribose polymer metabolism in limi ting carcinogenic events and the dependence of this metabolism on cell ular NAD levels predicts that niacin deficiency leading to reduced NAD levels may enhance carcinogenesis. This prediction has led us to init iate studies to evaluate the potential of niacin as a preventive facto r in human cancer. The first approach involves development of a method to assess biochemically niacin status in humans using intracellular N AD derived from whole blood, primarily erythrocytes, as the relevant m arker of niacin status. We have shown that erythrocyte NAD content var ies by as much as 12-fold within a population and can be modulated rea dily by supplementation. A second approach to testing this hypothesis involves understanding the relationship of dietary niacin, circulating levels of NAD precursors (nicotinamide and nicotinic acid) and NAD in target tissues for human cancer. Current analytical methods for quant ification of plasma levels of nicotinic acid and nicotinamide followin g intake in the dietary range are not sufficient. Thus, we have develo ped a CC-MS method for the rapid, sensitive, and selective determinati on of both nicotinamide and nicotinic acid in plasma. These methods wi ll now allow assessment of niacin metabolism in humans that could lead to a new understanding of niacin in prevention of cancer.