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D Medina

Publications and source records attributed to D Medina.

At least 163 records · Page 9Linked to original sources
PubMed1983

Selenium concentration and glutathione peroxidase activity in normal and neoplastic development of the mouse mammary gland.

This study was divided into three experiments. (a) The levels of selenium and glutathione peroxidase (GSH-PX) activity were determined for various developmental states of the mammary gland: normal (virgin, pregnant, and lactating); preneoplastic hyperplastic outgrowth lines; and neoplastic mammary tissues. Tissues from the pregnant and lactating mice had higher selenium concentrations and GSH-PX activities than did tissues from virgin mice, but the levels were similar to levels found in preneoplastic and neoplastic mammary tissues of lines C4 and D2. This suggests that the appropriate comparisons for studies determining the effect of selenium on preneoplastic mammary tissues are glands from pregnant and lactating mice. In addition, these results suggest that the refractory state of mammary tumors to selenium-mediated growth inhibition is not due to the absence of GSH-PX or the inability to incorporate selenium. (b) For the second experiment, the effect of feeding various levels of selenium on selenium and GSH-PX levels was determined in mammary and hepatic tissues of virgin mice. GSH-PX activity increased when dietary selenium increased from less than 0.02 to 0.1 ppm selenium but was not further increased when dietary selenium was above 0.1 ppm. (c) Finally, the mammary GSH-PX activity was evaluated at different concentrations of the substrates in order to document the biochemical characteristics of the mammary gland GSH-PX.

Aging↗
PubMed1983

Effects of combination estrogen:cyclophosphamide treatment on the growth of the MXT transplantable mammary tumor in the mouse.

The present studies were done to determine if the growth-promoting properties of estrogen on the MXT transplantable mammary tumor in the mouse would enhance the cytotoxicity of cyclophosphamide. Mice bearing these tumors had beeswax pellets implanted which contained 17 beta-estradiol (0.01 to 1.0 mg/pellet) and/or injected twice weekly with cyclophosphamide (10 to 40 mg/kg body weight in sesame oil) for 4 to 7 weeks. During this time, tumor size [(L + W)/2] and body weights were monitored every 7 to 14 days. The results show that administration of estradiol (0.01 to 1.0 mg/pellet) by implant slightly stimulated tumor growth, and in no case was tumor regression observed in response to the steroid. Likewise, cyclophosphamide treatment alone (10 to 20 mg/kg) failed to inhibit the tumor; however, combined administration of estradiol plus cyclophosphamide (10 to 40 mg/kg) resulted in significant inhibition of tumor growth. This response was time and dose dependent. These results show that while neither compound alone inhibited tumor growth, estradiol and cyclophosphamide are synergistic and completely block the growth of this transplantable mammary tumor in the mouse. The mechanism for this antagonism of mammary tumor growth remains to be resolved; however, we speculate that estradiol stimulates cellular hypertrophy and hyperplasia in these tumors, and under these conditions the cytotoxic effectiveness of cyclophosphamide is enhanced.

Animals↗
PubMed1982

Accelerated appearance of chemically induced mammary carcinomas in obese yellow (Avy/A) (BALB/c X VY) F1 hybrid mice.

Latent periods and cumulative incidence of mammary carcinomas (MT) up to 50 wk after initial gavage with 7.12-dimethylbenz[a]anthracene (DMBA) were determined in virgin yellow (Avy/A) and agouti (A/a) (BALB/cStCrlfC3Hf/Nctr X VY/WffC3Hf/Nctr-Avy) F1 hybrid female mice. When subcutaneous masses reached 5-10 mm in diameter, the mice were killed and necropsied, and the tissues examined histologically. No MT were found in control mice. Cumulative MT incidence in the 1.5-mg DMBA group (A) was 43% (41/95) among yellow mice, and 33% (32/96) among agoutis. In the 6.0-mg DMBA group (B), corresponding MT incidences were 86% (83/96) and 71% (67/95). In group A, the first percentile of MT detection was 13.0 wk after initial carcinogen treatment in yellow mice; it was 18.0 wk in agoutis. Corresponding latent periods for the 20th percentile were 34.3 and 47.0 wk. In group B, latencies for the first percentile were 8.3 and 9.0 wk. Corresponding latencies for the 20th percentile were 15.3 and 16.0 wk. Within genotypes and dose groups, rates of weight gain of mice that developed MT and those that did not were similar. We conclude that MT induced by low doses of DMBA arise more rapidly in yellow mice than in nonyellow littermates. The absence of spontaneous MTs, acceleration of chemically induced MT formation at a low dose level that does not induce general toxicity, and availability of genetically identical (except for one gene) normal control animals make this experimental system suitable for development of an assay to efficiently test the carcinogenic potential of low dose levels of chemical substances.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Differential effects of selenium on the growth of mouse mammary cells in vitro.

The effect of selenium was examined on the growth potential of normal, preneoplastic and neoplastic mammary cells grown in primary monolayer cell cultures and on 3 established mammary cell lines. Selenium, present as Na2SeO3 in serum-free DMEM, inhibited all mammary cell cultures at 1 x 10(-5) M. Selenium, at 5 x 10(-8) M, stimulated the growth of primary cell cultures of normal mammary cells and C4 preneoplastic cells and the established cell line YN-4, but not the growth of D2 preneoplastic cells and tumors in primary cell cultures and of established cell lines CL-S1 and WAZ-2t. The differential responses of cells from preneoplastic outgrowth lines C4 and D2 and of D2 primary tumors in vitro correlated with the sensitivity of these same cell populations to selenium-mediated inhibition of growth and tumorigenesis in vivo. The differential responses among the 3 cell lines will allow further comparative studies on the cell biological basis of selenium function.

Animals↗
PubMed1981

Selenium-mediated inhibition of 7,12-dimethylbenz[a]anthracene-induced mouse mammary tumorigenesis.

The effect of supplemental selenium on 7,12-dimethylbenz[a] anthracene (DMBA)-induced mammary tumorigenesis was investigated in several mouse strains. Selenium, administered as SeO2 in the drinking water, inhibited mammary tumor formation in DMBA-treated (C57BL x DBA/2f)F1, C3H/StWi and BALB/c female mice. In addition, selenium inhibited the occurrence of DMBA-induced ductal hyperplasias in (C57BL x DBA/2f)F1 and BALB/c mice and mammary tumour virus-induced alveolar hyperplasias in BALB/cfC3H mice. Selenium did not alter the growth of established mammary tumors. These results demonstrate that supplemental selenium inhibits both chemical-and viral-induced mouse mammary tumorigenesis, and secondly, that the development of preneoplastic lesions, an early stage in mammary tumorigenesis, is very sensitive to selenium-mediated inhibition.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Partial expression of endogenous mouse mammary tumor virus in mammary tumors induced in BALB/c mice by chemical, hormonal, and physical agents.

The possible interaction of environmental factors with the endogenous mouse mammary tumor virus (MMTV) genome in the development of mammary tumors in the low-tumor-incidence BALB/c mouse strain was examined. Tumors were induced in virgin female animals by treatment with chemical carcinogen 7,12- dimethylbenz[alpha]anthracene or urethan, with or without prolonged hormonal stimulation, or by X-irradiation. Concomitant hormonal stimulation resulted in increased tumor incidences compared with those induced by chemical carcinogen treatment alone. The frequency of tumor induction by irradiation alone or in combination with urethan or prolactin stimulation was very low. MMTV expression in the mammary tumors was assayed by nucleic acid hybridization and by immunohistochemical staining. Depending upon the treatment group, 0 to 89% of the tumors contained detectable levels of MMTV RNA (>/=0.0005% of the total cellular RNA). Tumors which contained detectable viral transcripts exhibited only low levels of MMTV RNA, which did not appear to represent the accumulation of RNA sequences homologous to the entire MMTV genome; synthesis of MMTV structural proteins was detected in only one tumor. Viral RNA-positive tumors were generally associated with a longer latent period. MMTV RNA expression occurred in tumors classified histologically as adenoacanthomas, as well as in mammary adenocarcinomas, although the cell types in the adenoacanthomas expressing viral RNA were not identified. It does not appear that expression of the endogenous MMTV genome is required for maintenance of all mammary tumors in BALB/c mice, although partial genome expression undetectable by the methods employed cannot be ruled out. Linear regression analyses were performed. The mean time to tumor appearance and the percentage of tumors which were MMTV RNA positive were found to vary linearly as a function of the total dose of 7,12-dimethylbenz[alpha]anthracene administered. The percentage of tumors which were MMTV RNA positive was also shown to be linearly related to the mean time to tumor appearance. These relationships provide a basis for predictions in the BALB/c system related to these parameters.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Estrogenic effects of nafoxidine on ovarian-dependent and independent mammary tumor lines in the mouse.

Nafoxidine (1-[2-[p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]ethyl]-pyrrolidine hydrochloride); a triphenylethylene derivative] and estradiol cause translocation of the estrogen receptor to the nucleus, elevate the levels of cytoplasmic progesterone receptors, and do not effect levels of nuclear progesterone receptor in hormone-dependent and -independent MXT-3590 mammary tumor lines. Cytoplasmic and nuclear receptor levels were measured by the dextran-coated charcoal assay and a modified protamine sulfate nuclear exchange assay, respectively. Both estradiol (2.5 microgram) and nafoxidine (40 microgram) stimulate partial growth in the independent line. These data are the first evidence of the estrogenic effects of a so-called antiestrogen (nafoxidine) on the quantity of progesterone receptors in a hormone-independent experimental mammary tumor. The growth effects of antiestrogens demonstrated here in ovariectomized mice should alert clinicians to be watchful of these effects when using such drugs in the treatment of human breast cancer. These results also confirm recent suggestions that growth and progesterone receptor synthesis are controlled separately by estrogenic compounds. (Endocrinology 108: 668, 1981)

Animals↗
PubMed1981

Effects of selenium on mouse mammary tumorigenesis and glutathione peroxidase activity.

The effects of supplemental selenium on 7,12-dimethylbenz(a)anthracene (DMBA)-induced and murine mammary tumor virus (MuMTV)-induced mammary tumorigenesis were investigated in BALB/c mice. Selenium (4-10 ppm), administered in the drinking water, inhibited mammary tumor formation in DMBA-treated mice. The higher doses of selenium (7-10 ppm) were tolerated well by the DMBA-treated mice and blocked mammary tumor formation by 80-90%. In addition, selenium at the lowest dose (4 ppm) inhibited the tumor-producing capabilities of a MuMTV-positive preneoplastic nodule outgrowth line by greater than 75%. The inhibition of tumor formation could not be attributed to an alteration in virus expression because there was no qualitative difference in the expression of of MuMTV proteins between selenium-treated and -untreated mice. Additionally, selenium-dependent glutathione peroxidase activity was detectable in normal virgin and preneoplastic mammary tissues of mice raised on a commercial diet and was increased 2-fold by 4 ppm supplemental selenium in the drinking water. These results demonstrate that supplemental selenium is an effective inhibitor of both chemical- and viral-induced mouse mammary tumorigenesis, and secondly, that the neoplastic transformation in, as well as the development of, preneoplastic lesions is sensitive to selenium-mediated inhibition.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Hormones and mouse mammary tumorigenesis.

The hormonal milieu of the host influences viral and chemical carcinogen-induced mammary tumorigenesis in a variety of indirect ways. The effects of a high-fat diet on mouse mammary tumorigenesis are very limited and are convincing only for ice infected by the high-oncogenic mammary tumor virus. The relationship between fat content in the diet, the hormonal milieu of the host, and mammary tumor virus function is unexplored.

Animals↗
PubMed1981

Preferential growth of mammary tumors in intact mammary fatpads.

Four transplantable tumors, three (66, 410, and 168cl) isolated from a spontaneously occurring strain BALB/cfC3H mammary tumor and one (D2) arising from a BALB/c hyperplastic alveolar nodule were found to grow better in mammary fatpads than at s.c. sites. Furthermore, tumor growth was better (p less than 0.05) in intact mammary glands than in cleared mammary fatpads for the D2, 410, and 66 tumors (168cl was not tested). The role of immunity in these differences was investigated using the highly immunogenic 410 tumors. Tumor 410 induced equally effective immunity to subsequent challenge whether it was implanted s.c. or in intact fatpads. Furthermore, in immunized animals, Tumor 410 was rejected equally well when the challenge site was intact fatpad as when s.c. Similarly, Tumor 410 induced immunity after implantation into cleared fatpads and, in immunized animals, was rejected when the challenge site was the cleared fatpad. We thus found no evidence that the mammary fatpad is immunologically privileged, as compared to the s.c. site, with respect to tumor transplantation antigens.

Adipose Tissue↗
PubMed1981

X-ray microanalysis of electrolyte content of normal, preneoplastic, and neoplastic mouse mammary tissue.

Intracellular sodium, chlorine, and potassium concentrations (mmol/kg dry weight) were determined by electron probe X-ray microanalysis of individual epithelial cells in freeze-dried 2-micrometer sections of mouse mammary tissue which were cut at -30 degrees. A model system was utilized in order to compare elemental content of cells from normal pregnant mammary tissue and preneoplastic and neoplastic mammary tissues from female BALB/cCrlMed mice. Animals were killed by cervical dislocation, and tissue was rapidly frozen in liquid propane. Normal mammary glands were obtained from primiparous mice at 16 to 17 days of gestation. Tissue from the hyperplastic alveolar nodule line D1 was removed from donor mice 12 to 16 weeks after transplantation into the cleared mammary fat pad. All mammary adenocarcinomas, D1T, were primary tumors which developed in mice with transplants of nodule line D1. Data were collected from five animals (10 cells/animal) in each of the three groups. It was found that the electrolyte content of cells of preneoplastic tissue was the same as that of the normal mammary tissue but was significantly elevated in neoplastic tissue (162, 130, and 48% increases for sodium, chlorine, and potassium, respectively). Thus, an increase in electrolyte content seems to be associated with the transformation to a neoplastic state and not associated with conversion to the preneoplastic state.

Adenocarcinoma↗
PubMed1981

Correlation of surface fucopeptide patterns with tumorigenicity of mouse mammary epithelial cells.

The plasma membrane fucopeptides of tumorigenic and nontumorigenic mouse mammary epithelial cells were studied. The types of cells analyzed included (a) cell lines derived from mouse mammary carcinomas of varying etiologies (viral, hormonal, chemical carcinogen), (b) a series of clonal cells lines which were nontumorigenic at lower passage levels and tumorigenic at higher passage levels, (c) normal primary cells derived from the mammary glands of pregnant or lactating animals, and (d) primary cells from tumors produced by s.c. injection of cultured mammary tumor cells into syngeneic animals. A distinctive difference was observed in the size distribution of the trypsin-sensitive surface fucopeptides from tumorigenic and nontumorigenic mammary cells; the tumorigenic cells were relatively enriched in the larger fucopeptides. The size distribution of the trypsin-sensitive surface fucopeptides was not markedly influenced by the physiological state of the cells or by cell population density. It appears that the trypsin-sensitive surface fucopeptide size pattern may be a distinguishing characteristic between tumorigenic and nontumorigenic mouse mammary epithelial cells.

Animals↗
PubMed1980

Characterization of a 7,12-dimethylbenz(alpha)anthracene-induced BALB/c mouse mammary tumor epithelial cell line.

Characterization of numerous independently derived cell lines is necessary in order to establish reliable biological criteria applicable to transformed mammary epithelial cells. A mammary tumor cell line (DMBA-2/BALB) and clonal derivatives have been established from an adenocarcinoma induced in vivo in a BALB/c mouse by the administration of the chemical, 7,12-dimethylbenz(alpha)anthracene. The parental and clonal lines in vitro, as well as tumors derived from them in vivo, maintained an epithelial morphology at the light microscope level. Electron microscopic observations demonstrated the presence of desmosomes and numerous microtubules and microfilaments, but low levels of rough endoplasmic reticulum and Golgi apparatus. Growth characteristics were examined, including saturation density levels and colony-forming ability on plastic and in suspension. None of the in vitro growth parameters was found to correlate with the tumorigenicity of the lines in syngeneic mice or with their ability to produce C- or B-type virions by reverse transcriptase assay. Peroxidase/antiperoxidase (PAP) immunological staining failed to detect virus-specified antigens, MuMTV gp52, Rauscher MuLV gp69/71, or BALB virus-2 gp70, in the cells. Although epithelial in appearance, the parental cell line did not appear to be functionally differentiated in culture as evidenced by a very low level of casein messenger RNA. Passage of the parental cell line in vivo in a lactating mouse failed to activate virus expression, but a few cells in scattered focal areas in the tumor did synthesize casein detectable by PAP staining.

9,10-Dimethyl-1,2-benzanthracene↗