title: Pharmacological intakes of niacin increase bone marrow poly(ADP-ribose) and the latency of ethylnitrosourea-induced carcinogenesis in rats.
abstract: Cancer chemotherapy agents cause short-term leukopenia during treatment and the development of secondary leukemias after recovery from the original disease. We reported that niacin deficiency in rats increases the severity of nitrosourea-induced leukopenia and the subsequent development of cancers. This study was designed to test the effects of supplementing an already high quality diet with pharmacologic levels of niacin. For a period of 4 wk, nontumor-bearing weanling Long-Evans rats were pair-fed AIN-93M diets that were niacin adequate (30 mg/kg diet) or pharmacologically supplemented (4 g/kg diet) with nicotinic acid (NA) or nicotinamide (Nam). One week after the initiation of niacin feeding protocols, ethylnitrosourea (ENU) treatment began (12 doses, 30 mg/kg by gavage, every other day). ENU treatment caused leukopenia, which was not prevented by niacin supplementation. At the end of ENU treatment, all rats were switched to a niacin-adequate diet and monitored. Within 36 wk after the start of treatment, all of the ENU-treated rats either lost 5% of peak body weight or had palpable tumors > 1 cm in diameter, and were necropsied. Supplementation with NA or Nam at 4.0 g/kg diet (combined analysis) increased the latency of the ENU-induced morbidity curve, relative to niacin-adequate controls. Morbidity could be attributed in almost all cases to some form of neoplasm, with leukemias the predominant form. In short-term studies, supplementation with either NA or Nam caused dramatic increases in bone marrow NAD(+) (1- to 1.5-fold), basal poly(ADP-ribose) (3- to 5-fold) and ENU-induced poly(ADP-ribose) levels (1.5-fold). These data show that supplementation of a niacin-adequate, high quality diet with pharmacologic levels of nicotinic acid or nicotinamide increases NAD(+) and poly(ADP-ribose) levels in bone marrow and may be protective against DNA damage.
authors.affiliation: Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Boyonoski
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Spronck
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jacobs
authors.forename: Girish M
authors.initials: GM
authors.lastname: Shah
authors.forename: Guy G
authors.initials: GG
authors.lastname: Poirier
authors.forename: James B
authors.initials: JB
authors.lastname: Kirkland
mesh_terms: D000477:Alkylating Agents; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005038:Ethylnitrosourea; D007970:Leukopenia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D009017:Morbidity; D009243:NAD / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology*; D009536:Niacinamide / Q000008:administration & dosage / Q000494:pharmacology*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
chemical_list: D000477:Alkylating Agents; D009243:NAD; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; D009525:Niacin; D005038:Ethylnitrosourea