Spontaneous Mammary Adenoma and Carcinoma in RIIIb Mice Deprived of Milk Agent

Abstract

THE suggestion was previously made that nodular adenomatous hyperplasia in mammary glands of mice of the RIII (Paris) strain, and possibly others, might provide a more sensitive and an earlier indication of the action of Bittner's milk agent than do actual tumours. Evidence obtained under experimental conditions of forced activation of the glandular response to combined influence of hormone and agent was givren in support of this suggestion. It seemed probable also that spontaneously occurring nodules as well as those forcibly stimulated would afford reliable evidence of the action of the agent. The validity of such evidence would depend upon complete absence of spontaneous adenomatous nodules in the same strain deprived of agent. In sublines of the RIIIX strain (renamed RIIb in accordance with international usage), which had been freed from agent by cross-suckling, no nodules had been found in the mammae of young unmated females forcibly stimulated, but two hyperplastic nodules were seen in 2 out of 44 females of the old breeding stock (Pullinger, 1947). Doubt thus arose whether the cross-suckled sublines were in fact entirely agent-free or whether, in old females, these nodules had some other cause. A survey of the mammae of all old females was in progress and was continued and combined with experiment in an endeavour to find an answer. The same problem, the stimulus for hyperplastic nodules in the Zb strain (C3H cross-suckled to deprive it of milk influence), was investigated by Huseby and Bittner (1946), who came to the conclusion that all three factors, namely the milk tumour influence, ovarian hormone and susceptibiltiy that are responsible for the development of heritable mammary tumours in mice are also necessary for the development of these alveolar hyperplasias. The same authors gave an account of the morphology of nodules found in the mammae of mice in former high cancer strains and their hybrids after deliberate exclusion of the agent by cross-suckling. The strains examined were C3H and A, designated Zb and AX. They compared the nodules with those in high cancer strains described by previous authors before knowledge of the milk agent existed. In the course of the present survey of old RIlIb (formerly RIIIX) breeders similar types of nodule were seen with the exception of those described as inflammatory. Focal acinar proliferations were often but not invariably discretely lobular. The squamous-celled nodules found in old RIIIb females have been described and their origins discussed (Pullinger, 1949).In relation to the problem of the presence and action of the milk agent these squamous-celled proliferations are not relevant, for it is generally agreed that tumours due to Bittner's agent are characteristically acinar formations and that