Forced Activation and Early Detection of the Milk-borne Agent of Mammary Adenomas in Mice

Abstract

THE presence and activity of the milk-borne agent of mammary tumours of mice discovered by Bittner (1936) are detectable only by the growth of a mammary tumour. No other criterion of its presence is yet generally accepted, though an opinion is widely held that certain localized nodular adenomatous mammary hyperplasias are an expression of the combined activity of the milk-borne tumour agent and a mammogenic hormone. Focal or nodular adenomatous hyperplasias in the mammae of dealer's mice were first described by Apolant (1906) and their cause investigated by Haaland (1911). Haaland inquired but failed to decide whether the nodules ( Fig. 1 and 2) were tumours from the beginning, or whether they were the basis from which tumours develop. Similar nodules occur in some inbred strains of mice. Thus Gardner, Strong and Smith (1939) found their incidence to be greatest in mice of the high cancer strains D and C3H, and intermediate in the low mammary tumour strain CBA and high mammary tumour strain A. Objections to accepting nodular hyperplasia as evidence of activity of the milk-borne tumour agent derive from two sources. In the first place these nodules-have occasionally been found in strains that do not develop mammary tumours. Gardner et al. found two nodules in one mouse out of nine of the N strain in which mammary tumours had never occurred. Also when efforts have been made to exclude the milk-borne agent from high cancer strains by cross-suckling, nodules have nevertheless been found. Thus Bittner, Huesby, Visscher, Ball and Smith (1944) examined the mammae of fostered breeding females (fostered by cancer-free maternal stock) from high cancer strains A and C3H. All the females had given birth to at least three litters and ranged from 11 to 16 months old, thereby providing suitable conditions for pathogenic activity of the milk-borne agent. Nodules were found occasionally, though never more than one to a gland, Thus nodules were still present though in smaller numbers when efforts were made to exclude them than in mice which had been suckled on their own cancer-prone mothers. This evidence indicated that nodule incidence is not eliminated by cross suckling with the same regularity that is attainable in regard to tumour incidence. Huesby and Bittner (1946) record that they found no nodules in the mammae of 6 virgin, and X per gland in 5 out of 12 breeding Zb females; none in 6 virgin and X per gland in one out of 12 breeding Strong AX females; none in 10 hybrid virgin females and per gland in 2 breeding females of the F.1 generation derived from these two strains, both deprived, previous to crossing, of the milk-borne agent.

Prostatic Metastasis to the Breast and the Role of Estrogens: Case Report and Review

“…Richardson (67) reported complete regression of stilbestrol‐induced acinar changes in male rats after the drug was discontinued. This confirmed prior studies by Fullinger (63), who found complete involution of the induced breast changes in male mice within twenty‐four to twenty‐eight weeks after cessation of therapy. A true malignant lesion, regardless of the type of etiologic influence, must endure after cessation of that influence.…”

“…The effect of estrogen therapy as a carcinogenic agent is also a question of great importance. It seemed pertinent, therefore, to review the literature on the subject (1–75), and to add the following case report…”

Squamous Differentiation in Mouse Mammae: Spontaneous and Induced

“…The R III X were bred by subsequent litter mating from one R III female and one male of the same litter which had been cross-suckled on a nursing C57 black mother in 1944 (Pullinger, 1947). In 228 breeders of this subline freed from the Bittner agent, the following spontaneous tumours have occurred: one mixed squamous and adenocarcinoma at 23 months old in a breeder spayed at 20 months; one unmixed squamous-celled carcinoma of mammary gland at 22 months in a mouse spayed at 20 months; one unmixed adenocarcinoma of the mammary gland at 19 months old in an intact animal; two sarcomas at 7 and 14 months old respectively; many lymphomas; many pulmonary adenomas and one carcinoma; one papilloma of the skin.…”

“…The mice here described had to be killed on account of large skin turnours, despite attempts to avoid them, before any mammary tumours had arisen. Early effects of methylcholanthrene on mammary epithelium were, nevertheless, sought for in accordance with a previous plan to determine the first morphological changes in cells that might be attributed to carcinogenic agents (Pullinger, 1940). It happened that in these young breeders foci of squamous differentiation exactly similar to those in the old untreated females were found but three times as often as in untreated mice and in greater numbers per mammary gland (Table III).…”