Enhancement of mammary tumor formation in mice by a cytostatic drug, melphalan.

Melphalan (L-phenylalanine mustard), a cytostatic drug used in treatment of human breast cancer, was injected into mice bearing preneoplastic hyperplastic alveolar nodule mammary outgrowth line D2. Melphalan, doses of either 2.5 or 5.

Mammary tumorigenesis in chemical carcinogen-treated mice. VI. Tumor-producing capabilities of mammary dysplasias in BALB/cCrgl mice.

Two types of mammary dysplasias occurring in 7,12-dimethylbenz[a]anthracene (DMBA)-treated BALB/cCrgl mice were transplanted into the cleared mammary fat pads of syngeneic mice for an assessment of their growth behavior and tumor potentials. Keratinized nodules, numerous in DMBA-treated, pituitary isograft-bearing BALB/cCrgl mice, produced primarily ductal outgrowth in control mice and very few tumors (7%) 56 weeks after transplantation. Such dysplasias transplanted into mice bearing pituitary isografts exhibited lobuloalveolar development and produced a higher incidence of tumors (32%).

Mammary tumorigenesis in chemical carcinogen-treated mice. IV. Induction of mammary ductal hyperplasias.

BALB/cCrgl, C57BL/Ki, and (C57BL/Ki X DBAf)F1 mice were treated with 7,12-diemthylbenz[a]anthracene (DMBA) or urethan to determine conditions that would induce a high frequency of ductal hyperplasias in the mammary gland. Among virgin BALB/c mice treated with either 3.0 or 4.

Preneoplastic lesions in murine mammary cancer.

The current model for murine mammary tumorigenesis indicates that discrete, morphologically identifiable preneoplastic lesions precede and give rise to mammary tumors. The hyperplastic alveolar nodule is the primary lesion that precedes and gives rise to mammary tumors in mice infected with the mammary tumor virus (Bittner) or its variants. In mice fed 7,12-dimethylbenzanthracene or urethan, hyperplastic alveolar nodules are present but infrequent, and the major mammary dysplasias present are ductal hyperplasias.

Mammary gland as a morphological end point in carcinogenesis studies.

The murine mammary tumor system is characterized by the presence of intermediate preneoplastic mammary cell populations. The intermediate mammary cell populations are characterized as either alveolar hyperplasias or ductal hyperplasias. The most frequently encountered preneoplastic cell population is the hyperplastic alveolar nodule, which has been extensively characterized with respect to its biological and hormonal properties.

Microcytotoxicity assay of immune responses to non-mammary tumor virus-induced, preneoplastic, and neoplastic mammary lesions in BALB/c mice.

Using a microcytotoxicity assay we have studied the immune responses to the preneoplastic, hyperplastic alveolar nodule (HAN) lines D1 and D2 and to the mammary tumors arising spontaneously from them in BALB/c mice. Lymph node cells (LNC) from mice bearing HAN implants, or from mice whose implants had been removed greater than 1 week prior to testing, failed significantly to inhibit survival of HAN cells in culture. Specific inhibition of HAN cells was found, however, in 9 of 28 experiments with LNC from mice whose implants had been removed within the week of testing, and not with LNC from sham-operated controls.

Hormone dependence and estradiol receptors in the D series of mammary nodule outgrowth lines and tumors.

Preneoplastic mammary nodule outgrowth lines were examined for their ability to grow and produce tumors in ovariectomized BALB/c mice. In addition, these nodule outgrowth lines and tumors derived from them were investigated for cytoplasmic estrogen receptor proteins by qualitative and quantitative techniques. Early ovariectomy, performed within 4 weeks after transplantation, slightly delayed but did not permanently block the ability of three different nodule lines to completely fill the fat pad with nodule tissue.

Gas contaminant inhibition of mammary gland differentiation in vitro.

A gas mixture of 95 percent 02/5 percent CO2 from several commercial sources was contaminated with a filterable substance (s) that inhibited mammary gland morphologic differentiation in vitro.

Nuclear magnetic resonance studies on human breast dysplasias and neoplasms.

The ability of nuclear magnetic resonance (NMR) spectroscopy to distinguish normal, diseased non-neoplastic, and neoplastic human breast tissues was investigated with T1 and T2 relaxation times used. The results indicated that NMR relaxation times could distinguish between the mean values of breast neoplasms and other diseased or normal tissues, with P values less than 0.001.

Unlimited division potential of precancerous mouse mammary cells after spontaneous or carcinogen-induced transformation.

Serial transplantation of normal mouse mammary gland in young, isogenic hosts results in progressive loss of division potential, and the transplant line is eventually lost. This is interpreted as an expression of senescence at the cell and tissue level, and it inevitably occurs even though experimental conditions for growth are judged to be optimal. An indefinite extension of mammary growth span can be accomplished by transformation of these normal cells into precancerous cell types, which grow as a benign tissue but which may, however, occasionally undergo a second transformation into a malignant carcinoma.

Distinction between the preneoplastic and neoplastic state of murine mammary glands.

We have, using nuclear magnetic resonance spectroscopy, measured the relaxation times and diffusion coefficient of water protons in primary mammary adenocarcinomas of mice. In our biological model, three morphological stages were defined: (a) mammary gland tissue from pregnant mice, (b) preneoplastic nodules, and (c) neoplastic tissue. It was found that neoplastic tissues could be distinguished from normal and prenoeplastic tissue.