Abstract A4: Protection against radiation-induced carcinogenesis

Abstract The rationale of this study stems from the concern of radiation-induced second malignancies after a course of definitive radiation therapy or the possibility of a terrorist-mediated nuclear attack resulting in large populations of people exposed to non-lethal radiation doses, which would substantially increase the risk for cancer induction post-exposure. Currently, there are no safe and effective interventions to reduce this risk to humans. Previous studies have shown that chronic administration of Tempol (nitroxide antioxidant) in the diet of mice results in decreased weight and spontaneous tumorigenesis, and increased tumor latency (Mitchell JB, et al., Free Radic Biol Med 34:93-102, 2003). In the current study we tested the hypothesis that Tempol (TP) administered in the diet of mice would reduce radiation-induced cancer when given after the radiation exposure. Total body radiation (3 Gy) was administered to female C3H and CBA mice. Along with various control groups, immediately after radiation one group of animals from each strain was placed on a TP diet. Food consumption and animal weights were monitored throughout the study. Animals were followed for their entire lifespan (>1300 mice). The endpoint for the study was tumor formation or until the animal reached a humane endpoint at which time the animal was euthanized and evaluated for the presence of tumor (pathology evaluated on all animals). TP food supplementation after radiation: a) did not alter food consumption compared to animals on a control food diet, b) compared to animals on control food diet, the TP diet resulted in decreased weights in both mouse strains (40% for C3H and 20% for CBA), and c) TP food supplementation post-radiation significantly enhanced the survival of both mouse stains. Median survival values for 0 Gy, 3 Gy, 0 Gy TP, and 3 Gy TP for C3H mice was 706, 434, 764, and 670 days, respectively. For CBA mice median survival values for 0 Gy, 3 Gy, 0 Gy TP, and 3 Gy TP for C3H mice was 901, 660, 939, and 782 days, respectively. The incidence of hematopoietic neoplasms (predominantly lymphomas) was significantly reduced in both mouse strains by TP treatment and both the onset and incidence of solid neoplasms was significantly reduced in CBA mice treated with TP. These results encourage more research on nitroxide-based antioxidants in the chemoprevention of cancer to elucidate the mechanism(s) involved. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A4.