Mammary Tumor Onset Research Articles

Chemoprevention of mammary tumor virus-induced and chemical carcinogen-induced rodent mammary tumors by natural plant products.

The natural plant products turmeric, beta-carotene, catechin, and betel leaf extract were evaluated for their antitumor effects on mammary tumorigenesis in murine mammary tumor expressing C3H (Jax) mice and in Wistar rats treated with the chemical carcinogen 7-12-dimethylbenz(a)anthracene (DMBA). Administration of turmeric through the diet and of beta-carotene, catechin, and betel leaf extract through the drinking water to virgin female C3H mice resulted in decreased tumor incidence and tumor burden. Administering 5% turmeric in the diet from 2 months of age showed suppression of mammary tumor virus-related reverse transcriptase activity and of preneoplastic changes in the mammary glands. Furthermore, feeding turmeric from 6 months of age resulted in a 100% inhibition of mammary tumors. In the DMBA model of rat mammary tumorigenesis, administration of turmeric, catechin, and betel leaf extract resulted in decreased tumor burden and tumor incidence, and a delay in the onset of mammary tumors.

Suppression of mouse mammary tumor proviral DNA and protooncogene expression: association with nutritional regulation of mammary tumor development.

Chronic energy intake restriction (CEIR) reduces mouse mammary tumor virus (MMTV)-induced mammary tumors in C3H/Ou mice. Fewer than 10% of C3H/Ou mice developed mammary tumors during 88 wk of study when subjected to CEIR regardless of calorie source (fat vs. carbohydrate). By contrast, 100% of mice fed ad libitum diets relatively high in fat or carbohydrate or a commercial diet developed tumors by 35-40 wk. MMTV proviral DNA transcription was shown to be activated in spleen, liver, lung, kidney, small intestine, and mammary gland of mice consuming these diets ad libitum. By contrast, these messages were suppressed by CEIR in all tissues analyzed except spleen. MMTV proviral messages in liver and mammary gland increased with age in full-fed mice and were suppressed by CEIR. These findings suggest that the nutritional regulation of MMTV proviral DNA expression is tissue-specific. In CEIR mice the suppressed MMTV proviral DNA transcripts in mammary gland and liver increased with time in association with the delayed onset of mammary tumors. Mammary tumorigenesis in C3H mice is associated with integration of MMTV proviral DNA, which appears to activate a putative mammary tumor protooncogene, int-1. CEIR apparently decreases the frequency of viral reintegration adjacent to the int-1 gene and thus inhibits expression of int-1 and probably an initiation step in mammary tumorigenesis. Expression of other putative protooncogenes, int-2 and ras, in liver tissue was also reduced by CEIR. These findings indicate that both initiation and promotion of mammary tumorigenesis are influenced by CEIR in C3H/Ou mice.

Effect of an estrogen antagonist (tamoxifen) on the initiation and progression of γ-irradiation-induced mammary tumors in female Sprague-Dawley rats

One hundred and sixty-eight female Sprague-Dawley rats were divided among 4 groups ( 42 rats/group) and were irradiated with 400 rad [ 137Cs ] γ rays to the whole body when 59 days old. The estrogen antagonist tamoxifen was injected s.c. daily from 29–89 days of age (Series 1) or from 89–149 days of age (Series 2), prior to the onset of palpable mammary tumors. Two groups of rats were injected with the diluent and served as controls. All rats were palpated bi-weekly for mammary tumors and killed 37 weeks after γ-irradiation. The number of mammary carcinomas which developed in each group and their significance levels were: series 1, controls, 31; tamoxifen treated, 11, P < 0.01; series 2, controls, 33; tamoxifen treated, 17, P < 0.01. Tamoxifen treatment did not significantly influence the incidence of benign mammary tumors (fibroadenomas) nor the rate of body weight gain. Thus, the effective use of an estrogen antagonist for the prophylaxis of radiogenic mammary carcinomas has been demonstrated in this study.

Selenium and the genesis of murine mammary tumors.

One hundred forty-seven female Sprague-Dawley rats were divided into 5 groups and at 60 days of age were treated i.g. with 5 mg of 7,12-dimethylbenzanthracene (DMBA) suspended in 1.0 ml of sesame oil. Selenium (Se), as selenium dioxide (SeO2), was administered in the drinking water to 4 of the 5 groups (30 rats/group) at 2 doses (2 and 4 mg/l) from 30-90 days of age (series 1) and from 90-150 days of age (series 2) prior to the onset of palpable mammary tumors. One group of rats (27 rats) served as controls. All rats were palpated weekly for mammary tumors and sacrificed 28 weeks after DMBA treatment. Total number of palpable mammary carcinomas which developed in each group were: controls, 60; series 1, 2 mg Se dose, 27, 4 mg Se dose, 29; series 2, 2 mg Se dose, 24, 4 mg Se dose, 32. Each dose level of Se in each series significantly (P less than 0.05) reduced the incidence of mammary carcinomas. These results provided evidence that Se can inhibit the early promoting phases of polycyclic hydrocarbon induced mammary carcinogenesis in female rats. Two hundred twenty-six nulliparous and 99 multiparous GR mice were treated daily with estrogen and progesterone for 13-16 weeks. Se (SeO2) was administered in the drinking water (2 mg/l) to one-half of these mice. Total number of mammary carcinomas in control nulliparous and multiparous mice were 119 and 90, respectively; in Se treated nulliparous and multiparous mice, 113 and 81, respectively. Se did not significantly effect mammary carcinoma incidence in hormone treated nulliparous and multiparous GR mice.

Mast cells and eosinophilic leukocytes in the formation of mammary gland tumors in female rats irradiated with ? rays at the age of 4 weeks

The onset of mammary gland tumors in female rats receiving a single dose of whole-body irradiation with γ rays in a dose of 200 R at the age of 4 weeks was studied. The first tumors were found in animals killed 6 months after irradiation, compared with at the 15th month after the beginning of the experiment in the control. All tumors found during the experiment in both irradiated and control rats were benign. Counting the mast cells and eosinophils in the mammary gland tissue showed a disturbance of the dynamics of the eosinophil content and a change in the mast-cell response during the course of radiation tumorigenesis.

Long-Term Effects of Neonatal Steroid Exposure on Mammary Gland Development and Tumorigenesis in Mice2

Newborn female mice of three strains--BALB/cfC3H [mammary tumor virus (MuMTV)-infected], BALB/c, and C57BL (both virus-free)--were given injections of 17beta-estradiol or testosterone, alone or in combination with ovine prolactin, for the first 5 days of life. Half of each group of mice were ovariectomized at 40 days of age, and all mice were killed between 6 and 16 months of age. Mammary glands of BALB/cfC3H mice receiving steroid hormones were better developed than those of mice not receiving steroids. Androgen induced a higher incidence of grossly dilated ducts and secretion-filled alveoli. Mammary nodule and tumor incidences were higher in steroid-treated mice than in controls; androgen resulted in higher incidences than did estrogen. The age of onset of mammary tumors was also earlier after neonatal steroid treatment. In BALB/c mice, neonatal injections of estrogen induced some alveolar development of the mammary gland; neonatal injections of ovine prolactin had a greater effect. The mammary glands of C57BL mice did not show any evidence of stimulation by neonatal hormone treatment, which indicated the probability of strain differences. However, no nodules or tumors occurred in these MuMTV-free strains. Therefore, MuMTV was essential for neoplastic mammary responses to neonatal hormone treatment. Ovariectomy prevented alveolar development and abnormal changes in the mammary glands of all groups, thus indicating that ovary-independent alterations in the mammary gland were not induced by neonatal steroid treatment. We concluded that neonatal steroid exposure resulted in increased mammary tumor risk in mice, but only in the presence of both MuMTV and ovaries.

Mammary Noduligenesis and Tumorigenesis in Pathogen-Free C3Hf Mice2

Mammary noduligenesis and tumorigenesis were studied in pathogen-free C3Hf/Sd female mice. The mice experienced a normal breeding regimen for up to 5 pregnancies, then were retired to live out their lifespan. Of 38 mice, 29 died of mammary tumors with a mean latent period of 700 days, 4 died of other neoplasms, and 5 died of non-neoplastic causes. It seemed that mice kept free from accidents or infectious diseases would ultimately develop neoplasms.The rate of mammary tumorigenesis in pathogenfree mice paralleled the rate of tumorigenesis in conventional mice. The high mammary tumor incidence reflected the fact that the whole population of mice survived long enough to develop such tumors. Thus, the low oncogenic potential noted for the nodule-inducing virus was related to the late age of onset of mammary tumors in C3Hf mice, rather than to the ultimate tumor incidence.-J Natl Cancer Inst S1: 961-965,1973.