Niacin status and treatment-related leukemogenesis

• Published in: Molecular cancer therapeutics Vol. 8; no. 4; pp. 725 - 732
• Main Author: Kirkland, James B
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01-04-2009
• Subjects: Animals; Antineoplastic Agents - adverse effects; Apoptosis - drug effects; Bone Marrow Cells - drug effects; Humans; Leukemia - etiology; Leukemia - metabolism; Leukemia - pathology; Niacin - administration & dosage; Niacin - deficiency; Niacin - physiology; Nutritional Status; Poly Adenosine Diphosphate Ribose - metabolism
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.MCT-09-0042

Chemotherapy often causes damage to hematopoietic tissues, leading to acute bone marrow suppression and the long term development
of leukemias. Niacin deficiency, which is common in cancer patients, causes dramatic genomic instability in bone marrow cells
in an in vivo rat model. From a mechanistic perspective, niacin deficiency delays excision repair and causes double strand break accumulation,
which in turn favors chromosome breaks and translocations. Niacin deficiency also impairs cell cycle arrest and apoptosis
in response to DNA damage, which combine to encourage the survival of cells with leukemogenic potential. Conversely, pharmacological
supplementation of rats with niacin increases bone marrow poly(ADP-ribose) formation and apoptosis. Improvement of niacin
status in rats significantly decreased nitrosourea-induced leukemia incidence. The data from our rat model suggest that niacin
supplementation of cancer patients may decrease the severity of short- and long-term side effects of chemotherapy, and could
improve tumor cell killing through activation of poly(ADP-ribose)-dependent apoptosis pathways. [Mol Cancer Ther 2009;8(4):725–32]