K. B. DeOme

The influence of host and tissue age on life span and growth rate of serially transplanted mouse mammary gland.

Abstract Mouse mammary gland has a finite life span when serially transplanted in isogenic female hosts, using declining rate of ductal growth as an indicator of aging. In the experiments reported here, young and old hosts were transplanted with mammary tissues from young and old donors, and the transplants were propagated serially until they were lost due to diminished capacity for growth. Mammary tissue derived from both young and old donors behaved similarly when propagated in young hosts, and no consistent effect of donor age was observed. Old hosts, in contrast, did not support vigorous growth of either old or young grafts, probably because of endocrine insufficiency. The lack of vigorous growth during the first transplant generation in old hosts did not reduce the growth potential of either young or old transplants, since both grew well when retransplanted into young hosts. The results suggest that the life span of mammary cells is primarily related to a limited potential for division.

Growth of Mouse Mammary Glands in vivo after Monolayer Culture

Mouse mammary tissue grown in primary cell culture did not display specialized characteristics of the parent tissue. When implanted into gland-free mammary fat pads, not only did some of these cultured cells grow and produce normal mammary outgrowths, but some of the outgrowths formed glands which displayed a variety of culture-induced abnormalities.

The influence of mammogenic hormones on serially transplanted mouse mammary gland.

Abstract Mouse mammary gland, which shows a progressive decline in rate of ductal growth during serial propagation in vivo , was passaged in both normal virgin hosts and in hosts bearing pituitary isografts. In both groups ductal proliferation declined, and there is no evidence that the mammogenic stimulation provided by additional pituitaries prevented loss of ductal growth potential. In the pituitary-stimulated group, it was found that alveolar proliferation, which was conspicuous in early transplant generations, also declined with age. Finally, mammary gland was propagated in normal virgins without pituitaries until ductal growth was slowed, and a single exposure to alveolar-mammogenic stimulation was provided by breeding. Alveolar proliferation was then normal and extensive, but ductal elongation was not stimulated. These results suggest that aging of mammary cells, when measured by reduced growth potential, occurs because of declining ability to respond by proliferation to any set of endocrine stimuli that is constant and which continues over a long period of time. The ability of gland which is aged under one particular set of humoral conditions to proliferate in response to another, different set, suggests that the observed aging effect represents progressive alterations to hormone-responsive regulatory mechanisms, and does not indicate a permanent inability of mammary cells to divide.

A new approach to mammary tumorigenesis in rodents.

Most of the mammary tumors in mice and rats arise from recognizable lesions of the mammary gland. The nodule cells are subpopulations of mammary cells which resemble the normal lobules of pregnant mice. They are considered preneoplastic lesions. At least 2 sequential transformations in the process of mammary tumorigenesis occur. The 1st is a change from normal to nodule and the 2nd is a change from nodule to tumor. Experimental material consisted of hyperplastic alveolar outgrowth lines which did not carry the mammary tumor virus MTV or its variant NIV and were not induced by chemical carcinogens or by irradiation. The primary nodules from which the outgrowth lines were developed occurred in BALB/cCrgl and BALB/cAnDe female mice. The BALB/cCrgl donors had been subjected to prolonged hormonal stimulation from pituitary isografts. The others were retired breeders. The tumor incidence of untreated nodule outgrowths maintained in intact BALB/c virgin females varied from 4% to 61%. Ages of onset varied from 8 to 13 months. Oncogenic agents studied with BALB/cCrgl mice were MTV NIV 3-methylcholanthrene (MC) 9 10-dimethyl-1 2-benzanthracene (DMBA) urethan gamma radiation and prolonged hormonal stimulation. These agents induced nodule transformation when applied to the hormonally stimulated female BALB/c mice. Results showed that MTV and NIV were effective agents in neoplastic transformation. MTV was more effective. MC and DMBA and urethan were also effective agents. Gamma radiation produced a small but significant increase in the incidence of tumors and the latent period was reduced. It was thought that attention should be focused on conditions leading to the nodule transformation as well as to the neoplastic transformation. Ability to manipulate the hosts immunologic defense mechanisms should be directed toward the nodule cell population rather than to the already established neoplastic cell population.

Mammary tumor development in transplanted hyperplastic alveolar nodules of the mouse.

Summary Nodules from adult C3H/Crgl females produce a high incidence of mammary tumors following transplantation into young females. On the other hand, nodules from two C3H sublines which lack demonstrable biologically active mammary tumor virus (MTV) rarely develop mammary tumors when similarly transplanted. Simple exposure to MTV (achieved by transplanting nodular outgrowth from the MTV-free sublines into MTV-infected C3H/Crgl hosts) does not create tumor potentials in these outgrowths equivalent to those seen in the C3H/Crgl population of nodules. It is concluded that a different population of nodules (with regard to tumor potential) is formed in the absence of the MTV than in its presence.

Localization of casein-rich, fat-rich and DNA-synthesizing cells in monolayer cultures of mid-pregnant mouse mammary epithelium.

SynopsisMonolayers of 16-day pregnant BALB/cfC3H/Crl mouse mammary epithelial cells were examined for the occurrence and distribution of cells which contain large amounts of casein and fat and those which synthesize DNA. Cells within the central portions of colonies of epithelial cells appeared rich in casein and fat, whereas cells on the peripheral edges of the colonies synthesized DNA almost exclusively. Casein deposits and DNA synthesis were mutually exclusive phenomena, since only 2% of the cells synthesizing DNA also stained for casein. Of the casein-rich cells, 74% were also rich in fat, suggesting that cells which contain large deposits of casein almost always contain large amounts of fat. These results indicate that a specialization of function exists between cells on the growing edge and those centrally located within a single colony of nammary epithelial cells.

Radiophosphorus Uptake by Normal, Hyperplastic, and Tumorous Mammary Tissues of Mice.

Summary The hyperplastic nodule of the nonpregnant C3H/He mouse mammary gland shows a radiophosphate (P32) uptake intermediate between that of normal and tumorous mammary tissue. The relative P32 incorporation (tumor > hyperplastic nodule > normal) was not appreciably affected by any of a series of endocrine manipulations (ovariectomy; androgen, estrogen, or cortisol administration). However, during the second half of pregnancy, the uptake by both normal and hyperplastic tissues increases.

Mammary tumor virus activity in mammary tissues of hormone-stimulated balb/cfc3h/crgl mice.

Summary Hormonal stimulation leads to early MTV activity in the mammary glands of BALB/cfC3H female mice. Whereas substantial MTV activity does not appear until 13 weeks in the intact virgin BALB/cfC3H mammary gland, 3 weeks of hormonal stimulation leads to MTV activity in mammary ducts of 6-week-old BALB/cfC3H female mice. In addition, both BALB/c normal lobules and BALB/c hyperplastic nodule outgrowths possess MTV activity after 6 weeks in a MTV-positive host, following 3 or more weeks of hormonal stimulation.