Mammary carcinogenesis in rats after X- and neutron irradiation and hormone administration

The relatiely high estimates of the incidence per unit dose of radiation-induced breast cancer in women are derived from a few studies on groups of women who were exposed to large doses of radiaton. In view of the implications of these observations for the risk estimates of low dose exposures, such as those employed in mammography, it is of great importance to obtain quantitative information on the dose-effect relationships for mammary gland carcinogenesis in experimental models. Three rat strains, Sprague-Dawley (SD), Wistar WAG/Rij and Brown Norway (BN), with expected different susceptibilities for the induction of mammary cancer, have been irradiated with 300 kV X-rays and mono-energetic neutrons with energies of 0.5, 4 and 15 MeV. For each type of radiation and different dose levels four subgroups have been included in the study, intact females, intact females treated with oestrogen, hystero-ovariectomized females and hystero-ovariectomized females treated with oestrogen. Increased hormone levels were obtained by subcutaneous implantation of pellets with oestradiol-17β (E2). A total of 5000 animals are included in the study. In the irradiated groups the first tumours generally appeared between 10 and 12 months after irradiation. For the non-irradiated control groups the latent period is considerably longer (e.g. 21.5 months in the Sprague-Dawley). The cumulative mammary tumour induction is presented as a function of radiaton quality, absorbed dose and time after exposure. The dose effect curves derived from these data are used to determine the relative biological effectiveness (RBE) for the different neutron beams. The preliminary results of this study indicate that there are considerable differences in susceptibility for tumour induction by ionizing radiaton in the three rat strains.