OCCURRENCE OF MAMMARY-TUMORS IN BEAGLES GIVEN RA-226

A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with Ra-226 at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 15 6 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs a nd 59 of 61 dogs given Ra-226 survived the minimum age for diagnosis o f mammary tumors of 3.75 years. Based on the observed age-dependent tu mor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in t he radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indica ted no increased risk for the first tumor occurrence in irradiated dog s. Cox regression analysis of the multivariate risk sets showed no sig nificantly increased risk for the occurrence of benign tumors but a st atistically higher risk of 1.66 with a confidence interval of 1.15-2.4 0 for the occurrence of malignant tumors. The increased risk was depen dent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized do gs at time of surgery decreased the relative risks slightly but did no t alter the significance. Exposure to diagnostic X rays with cumulativ e exposures below 0.2 Gy had no effect on tumor formation. It is unkno wn whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irra diation of fatty mammary tissue from transient radon-->polonium deposi tion, or a general effect of the overall radium deposition on the immu ne system of the dogs that lowered their resistance to formation of ma mmary tumors. Results of this study are potentially useful in understa nding risks of radium-induced breast cancers in humans.