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Article

Niacin Deficiency in Rats Increases the Severity of Ethylnitrosourea-Induced Anemia and Leukopenia¹

Ann C. Boyonoski², Lisa M. Gallacher², Michèle M. ApSimon^*, Robert M. Jacobs, Girish M. Shah^**, Guy G. Poirier and James B. Kirkland^*2

^* Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1; ^** Laboratory for Skin Cancer Research, Laval University Medical Research Center, CHUQ, Faculty of Medicine, Laval University, 2705 Laurier Blvd., Sainte. Foy, Quebec, Canada G1V 4G2; and Unit of Health and Environment, Hospital Research Center of Laval University, Sainte. Foy, Quebec, Canada G1V 4G2

²To whom correspondence should be addressed.

Many chemotherapeutic agents function by damaging the DNA of rapidly dividing cells, leading to side effects in the bone marrow, including anemia and leukopenia during chemotherapy and the development of secondary leukemias in the years following recovery from the original disease. We have created an animal model of alkylation-based chemotherapy, in nontumor-bearing rats, to investigate the effect of niacin deficiency on the side effects of chemotherapy [2 x 2 design, niacin-deficient (ND) vs. pair-fed (PF) control, and ethylnitrosourea (ENU) vs. vehicle control (C)]. Weanling Long-Evans rats were fed ND diet or PF niacin replete diet for 4 wk. ENU or C treatment started after 1 wk of feeding and consisted of 12 doses delivered by gavage, every other day. At 4 wk postweaning, niacin deficiency and ENU treatment ended, the rats were fed a high-quality control diet (AIN-93M) and the recovery of blood variables was monitored. ND alone decreased growth rate and caused anemia and neutrophilia. ENU treatment alone caused anemia, lymphopenia, neutropenia and an increase in circulating reticulocytes. In combination, ND and ENU treatment synergistically decreased hematocrit. ND prevented the ENU-induced increase in reticulocyte numbers observed in control rats. ND also increased the severity of ENU-induced lymphopenia. A combination of ND and ENU abolished the neutrophilia caused by ND alone. In summary, ND significantly increased the susceptibility of young Long-Evans rats to ENU-induced bone marrow suppression, suggesting that niacin-deficient cancer patients may benefit from supplementation.

KEY WORDS: • rats • niacin • nitrosourea • leukopenia • anemia

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