Effect of high-dose, fractionated local irradiation on MNU-induced carcinogenesis in the rat mammary gland

The effect on chemical carcinogenesis in the mammary gland of high-dose fractionated, local irradiation, as is used in the treatment of human breast cancer, was examined in a rat model of this disease process. For this purpose, a highly reproducible method was employed for administering a therapeutic dose and fractionation schedule via an anterior portal to a single mammary gland chain of rats in a manner that minimized whole body irradiation. This approach offers significant advantages over whole body irradiation techniques previously used for investigations of radiation mediated effects on the carcinogenic process. Among the advantages are that higher doses of radiation can be administered to the target tissue with minimal side effects and that the contralateral mammary gland chain can serve as a ‘within animal control’. When this approach was used to study the effect of high-dose fractionated radiation on the risk of development of mammary cancer in rats given 1-methyl-1-nitrosourea prior to radiation, an enhanced tumorigenic response was observed that greatly exceeded the response resulting from either radiation or carcinogen administered alone. This result was unanticipated, based on data from animal studies of the effects of whole body irradiation on mammary tumor development and the outcome of clinical series. Possible reasons for the discrepancy are presented.