Bartstra, R. W., Bentvelzen, P. A. J., Zoetelief, J., Mulder, A. H., Broerse, J. J. and van Bekkum, D. W. The Effects of Fractionated Gamma Irradiation on Induction of Mammary Carcinoma in Normal and Estrogen-Treated Rats.
The effects of dose fractionation on induction of mammary carcinoma were studied in normal and estrogen-treated female rats of the inbred WAG/Rij strain. Groups of 40 animals received total-body doses of 1 or 2 Gy of 137Cs γ radiation, administered in fractions of 2.5, 10 or 40 mGy with intervals of 12 h, or in fractions of 10 mGy with intervals of 2, 5 or 24 h. The irradiations were started at the age of 8 weeks. Estrogen treatment was accomplished by implantation of a pellet containing estrogen at the age of 6 weeks. All mammary tumors were resected and classified histologically as carcinoma or fibroadenoma. The age-specific incidence of mammary carcinoma was compared with that in control groups of unirradiated normal or estrogen-treated rats and was expressed as excess normalized risk, using lifetime statistical analysis with both parametric and nonparametric methods. The data were also compared to the results of single-dose experiments reported in previous papers. Fractionated irradiation increased the risk of mammary cancer in both normal and estrogen-treated rats compared to the corresponding unirradiated control group. The excess normalized risk per unit of total dose was approximately equal with or without estrogen treatment. Without estrogen treatment, the effects of the single-dose and fractionated irradiations were approximately equal. In estrogen-treated animals, however, single-dose irradiation was up to 15 times more carcinogenic than the fractionated exposures. This fractionation effect appeared to vanish for total doses below approximately 0.3 Gy. With estrogen treatment, the excess normalized risk was significantly higher for dose fractions of 40 mGy than for fractions of 10 mGy. The risk was also markedly higher for fractionation intervals of 2 or 5 h than for intervals of 12 or 24 h. The results of these experiments show that the effects of dose fractionation on the induction of mammary carcinoma may depend on hormonal status, the total dose delivered, the dose per fraction, and the fractionation interval.
