Factors observed to modify mammary carcinogenesis from low doses of low and high LET radiations in the Sprague-Dawley rat

The probability of cancers developing after exposures to low doses of radiation is important knowledge, both for risk assessments for environmental exposures on Earth and in Space, and for the determination of normal tissue tolerances in radiation therapy. The few comprehensive, lifetime studies of in-vivo responses, especially to energetic heavy ions, report tumorigenesis rather than carcinogenesis, with the majority of tumors being benign. To fill this gap of data for carcinogenesis, our group has been examining carcinogenesis in Sprague-Dawley rats exposed to megavoltage gamma rays, energetic protons, and energetic heavy ions. Four cohorts of female Sprague-Dawley rats were exposed to cobalt-60 gamma rays, cesium-137 gamma rays, 250-MeV protons, and 1-Gev iron ions at doses beginning at 5 cGy for the iron ions and 50 cGy for the gamma rays and protons. We have been examining the morphology of the tumors and tissues. We have observed a correlation between the risk of mammary cancers and specific genetic, cytogenetic, epigenetic, and abscopal factors; our group has correlated the risk of mammary cancers after irradiation in this animal model with the status of the pituitary, the ovaries, and the estrous cycle, as well as with caloric intake, and these results will be summarized. We had postulated that even for low doses of highly ionizing radiations, the risk might be reduced after the animals were exposed by the administration of anti-estrogens. We administered Tamoxifen to the animals for their lifetimes beginning four weeks after exposure. The incidence, the change in incidence with the administration of Tamoxifen, and the histopathology of radiation/Tamoxifen resistant malignancies will be presented