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WHEN 5 ,ig. of oestrone alone or combined with 50 ug. of progesterone were substituted weekly for 60 weeks after bilateral ovariectomy in RIIIf strain mice in which no evidence of milk factor has been found through 49 generations after cross-suckling, mammary carcinoma incidence was raised from none in intact virgin females to 1 in 39. In ovariectomised breeders the spontaneous incidence of 1 in 40 in intact females was maintained at about the same level, 1 in 31, by substitution of 5,g. oestrone weekly after breeding. 50,g. weekly failed to induce any carcinoma in 37 ovariectomised breeders. Owing to the low spontaneous incidence in RIIIf mice and therefore the large number of females that would be required, it was not feasible to try to determine whether or not bilateral ovari-ectomy after breeding would prevent the appearance of mammary carcinoma in later age (Pullinger, 1955, 1957). Other problems that could not be pursued for the same reason and also on account of a large increase in incidence of lympho-blastoma, concerned the variety in kind and quantity of other natural hormones and their metabolites which might be substituted. Would substitutions of oestradiol; oestriol or other biologically active metabolites or mixtures of these with oestrone give similar results? Is there a quantitative relationship between naturally occurring ovarian hormones and mammary carcinoma incidence in mice without milk factor? or is there a maximum incidence for each agent free strain, which can be reached but not exceeded whatever the dose of natural oestrogen whether endogenous or applied? Thanks to the generous gift to this hospital by Dr. W. E. Heston of 2 litters of C3Hf/He mice it has been possible to continue this enquiry using another strain. Whereas the highest spontaneous incidence of mammary carcinoma seen in RIIIf breeding females was between 2 and 3 per cent after 1 year of age having borne at least 3 and up to 16 litters, the spontaneous incidence of C3Hf/He breeders lacking evidence of milk factor was originally 38 per cent. At the time the 2 litters in the F 24 and 25 generations were received in 1954 the incidence had recently fallen. It has in the interim been found to have an overall value from F 6 to F 25 of 22 per cent (Heston, 1958). Particulars of origin, of cross-suckling after delivery by Caesarian section, of the subsequent examination of characters and of tests for …

Mammary Carcinoma Incidence in C3Hf Virgin Female Mice after Ovariectomy and Substituted Oestrone