Niacin status and treatment-related leukemogenesis

Abstract

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.