title: Niacin supplementation decreases the incidence of alkylation-induced nonlymphocytic leukemia in Long-Evans rats.
abstract: Niacin deficiency impairs poly(ADP-ribose) formation and enhances ethylnitrosourea (ENU)-induced carcinogenesis. Previous experiments were compromised by rapid progression of cancer, and the current study was designed with half the number of ENU doses. Weanling male Long-Evans rats were fed niacin deficient (ND), pair-fed (PF) control (30 mg nicotinic acid/kg), or pharmacological niacin (NA; 4 g nicotinic acid/kg) diets. After 2 wk, rats were gavaged every other day with ENU [30 mg/kg body weight (bw)] or vehicle (6 doses). Four days after the last dose of ENU, all rats were switched to AIN-93M diet and mildly feed restricted to maintain a constant food intake per bw. Rats were monitored for termination criteria and assessed for cancer development. Total cancers developed more rapidly in rats on the ND diet compared to those receiving high dose supplements of NA (P = 0.02; Gehan's generalized Wilcoxon test). Importantly, all of these differences occurred in the leukemias, especially the nonlymphocytic leukemia fraction (P = 0.008; Gehan's generalized Wilcoxon test), with incidences of 36%, 17%, and 11% in ND, PF, and NA rats, respectively. Because nonlymphocytic leukemias represent the majority of secondary cancers, these data support the concept that niacin supplementation may help protect cancer patients from the deleterious side effects of chemotherapy.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Anne-Pascale
authors.initials: AP
authors.lastname: Bartleman
authors.forename: Robert
authors.initials: R
authors.lastname: Jacobs
authors.forename: James B
authors.initials: JB
authors.lastname: Kirkland
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D019587:Dietary Supplements; D005038:Ethylnitrosourea / Q000633:toxicity; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D009374:Neoplasms, Experimental / Q000453:epidemiology / Q000517:prevention & control*; D009525:Niacin / Q000494:pharmacology*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D016588:Anticarcinogenic Agents; D011064:Poly Adenosine Diphosphate Ribose; D009525:Niacin; D005038:Ethylnitrosourea