More about mammary tumors in beagles given radium-226.

A recently published paper from this laboratory (1) reported an excess of malignant mammary tumors among female beagles injected with 226Ra as compared with female control beagles (among 226Ra dogs, there were 34 expected and 66 observed, P < 0.005). A corresponding excess was not seen for benign mammary tumors. There seemed to be no difference between dogs given 226Ra and controls in the appearance time for the first malignant mammary tumor, but there was an indication that the timing of subsequent mammary cancers (three or more per animal) was affected by 226Ra exposure. Neither ovariectomy nor exposure to diagnostic X rays could be shown to be associated with the difference between controls and dogs given 226Ra with regard to mammary malignancies. It was proposed in that report (1) that the increased risk of mammary cancer might have been a result of (a) initial deposition of 226Ra in sensitive tissue, or (b) transient deposition of 226Ra progeny in the mammae, or (c) a general effect on the immune system of skeletal a-particle irradiation by radium and its progeny that might reduce the resistance to expression of mammary neoplasia. Since our report was accepted for publication, we have had the opportunity to examine the mammary tumor experience among comparable female beagles given injections of either 241Am or 239pu. Both of these radionuclides are a-particle emitters and also irradiate the skeleton. However, no such differences in mammary tumor frequency between dogs given 241Am or 239pu and controls could be detected. These data have some relevance to the third of the three possibilities given above that were discussed by Bruenger et al. (1). Reports dealing with the analysis of soft-tissue tumors in our beagles given 241Am or 239Pu have been submitted for publication or are in preparation. Not included in the published version of our paper on mammary tumors in dogs given 226Ra was an analysis of the comparison between irradiated beagles and controls with respect to the number of separate dates on which mammary tumors were diagnosed in the individual animals. An excess of malignant tumors in the dogs given 226Ra could have been a result of (a) a greater average number of dates on which tumors were diagnosed, (b) a larger average number of tumors diagnosed at each diagnosis date or (c) a combination of both (a) and (b). Table I exhibits the results of this comparison. It appears from the data in Table I that there cannot be established a difference in the average number of dates on which tumors were diagnosed between controls and irradiated animals: Therefore, it seems more probable that the observed difference in the number of malignant tumors reported by Bruenger et al. (1) may have been a result of a larger average number of tumors diagnosed in 226Ra dogs on any one day. For many years, it has been the policy of our group to use the word "dose" to denote the energy imparted to matter and to designate a corresponding value that has the units of gray or rad, exclusively. To avoid confusion, we have tried (not always successfully) to use the word "dosage" to denote such other concepts as the amount of radioactivity adminis-