Radiation carcinogenesis of the rat mammary gland was investigated with the objective of investigating the combined effect of oestrogen administration and irradiation. Three rat strains, Sprague-Dawley, Wistar WAG/Rij and Brown Norway, with different susceptibilities to the induction of mammary cancer, have been irradiated with X-rays and mono-energetic neutrons. Increased hormone levels were obtained by subcutaneous implantation of pellets with oestradiol-17 beta (E2). The tumour incidence results were corrected for competing risks and were analysed with a continuous failure time distribution. The latency period for the hormone-treated animals is considerably shorter than for animals with normal endocrinological levels. Administration of the hormone results in an appreciable increase in the proportion of rats with malignant tumours. At the level of hormone administration applied in this study, radiation and hormones appear to produce an additive effect. The effect of hormone administration and irradiation for mammary tumourigenesis is equal for hormone administration one week prior to, or 12 weeks after irradiation. The RBE values for induction of mammary carcinomas after irradiation with 0.5 MeV neutrons have a maximum value of 20 and are not strongly dependent on the hormone levels.

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Cancer induction is generally considered to be the most important somatic effect of low doses of ionizing radiation. It is therefore of great concern to assess the quantitative cancer risk of exposure to radiations of different quality and to obtain information on the dose-response relationships for carcinogenesis. Tissues in the human with a high sensitivity for cancer induction include the bone marrow, the lung, the thyroid and the breast in women. If the revised dosimetry estimates for the Japanese survivors of the atomic bomb explosions are correct, there is no useful data base left to derive r.b.e. values for human carcinogenesis. As a consequence, it will be necessary to rely on results obtained in biological systems, including experimental animals, for these estimates. With respect to radiation protection, the following aspects of experimental studies on radiation carcinogenesis are of relevance: Assessment of the nature of dose-response relationships. Determination of the relative biological effectiveness of radiations of different quality. Effects of fractionation or protraction of the dose on tumour development. For the analysis of tumour data in animals, specific approaches have to be applied which correct for competing risks. These methods include actuarial estimates, non-parametric models and analytical models. The dose-response curves for radiation-induced cancers in different tissues vary in shape. This is exemplified by studies on myeloid leukaemia in mice and mammary neoplasms in different rat strains. The results on radiation carcinogenesis in animal models clearly indicate that the highest r.b.e. values are observed for neutrons with energies between 0.5 and 1 MeV. On the basis of such results it might be concluded that the maximum quality factor of 10 for neutrons should be increased. Based on current evidence, an increase by a factor of 2 to 3 seems more realistic than a tenfold rise. The diversity of dose-response relationships point to different mechanisms involved in the induction of different tumours in various species and even in different strains of the same species.

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