Protection against Radiation-Induced Carcinogenesis

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Radiation-induced accidents of terrorist-mediated nuclear attack resulting in large populations of people exposed to nonlethal radiation doses could increase substantially the risk for cancer induction after exposure. There are no safe and effective interventions to reduce this increased cancer risk to humans. A number of publications have shown that immune activation can be inhibited by rapamycin. Rapamycin targets mTORC1 leading to mTORC12 inhibition. Rapamycin also plays a role in inhibiting T cell activation and hence, rapamycin has important immunosuppressive properties. When rapamycin was administered chronically in mouse chow, mice had extended lifespans and the appearance of spontaneous cancers was delayed. Kaplan-Meier survival for C3H mice exposed to 3 Gy total body irradiation followed by treatment with or without various concentrations of rapamycin in the mouse chow was conducted. Compared with 3 Gy alone, rapamycin (140 mg/kg) in the mouse chow after 3 Gy resulted in significant survival increase and reduction of carcinogenesis. These results suggest that rapamycin and most likely other rapalogs, should be considered for use after unexpected total body radiation or after a course of radiation therapy to decrease the cancer incidence of incidence of secondary malignancies, respectively. (See Publications below)