PubMed Health⌕ Search

Biomedical subjects

J Russo

Publications and source records attributed to J Russo.

At least 253 records · Page 14Linked to original sources
PubMed1983

Susceptibility of the mammary gland to carcinogenesis. III. The cell of origin of rat mammary carcinoma.

The rat mammary gland epithelium is composed of three cell types: dark cells (DCs), intermediate cells (ICs), and a layer of myoepithelial cells (MCs), which are evenly distributed along the mammary gland tree in rather constant proportions. The present study was carried out for a determination of the effect of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) on the distribution and proliferative activity of these cell populations. The proportion and the DNA labeling index (DNA-LI) of each cell type were determined in terminal end buds (TEBs), terminal ducts (TDs), alveolar buds (ABs), and alveoli of the normal Sprague-Dawley rat mammary gland and in intraductal proliferations (IDPs) and carcinomas removed at selected intervals after DMBA administration. DMBA-induced changes in cell distribution were limited to TEBs and TDs, whereas ABs and alveoli were unaffected. The alterations consisted in an increment in ICs from 11% in TEBs and TDs to 90% in tumors and a decrease in DCs from 77% in TEBs and TDs to 7% in tumors. MCs were relatively unaffected. The DNA-LI of DCs, which in the normal gland TEB was 14%, was depressed by DMBA to 6%, whereas the DNA-LI of ICs remained unchanged from the basal level of 40% during the process of carcinogenesis. The progressive increment in number of ICs with a steady DNA-LI suggested that the IC is the target cell of the carcinogen and the cell of origin of mammary carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Blood vessel invasion and axillary lymph node involvement as prognostic indicators for human breast cancer.

Blood vessel invasion and axillary lymph node involvement were examined in 175 breast cancer patients. The incidence of blood vessel invasion was 35%. The presence of blood vessel invasion was highly associated with early disease recurrence. The association of poor prognosis with blood vessel invasion was independent of clinical stage, menopausal status, node status, tumor size, or postsurgical treatment. Those patients with blood vessel invasion and two or more positive nodes were at extremely high risk for early recurrence (70% recurrence by two years compared with 15% recurrence in the remainder of the patients). Thus, blood vessel invasion is a useful indicator of early recurrence in patients with primary breast cancer and, in combination with node status, is a prognostic indicator with high discriminatory power.

Axilla↗
PubMed1982

Differentiation of the mammary gland and susceptibility to carcinogenesis.

It has been demonstrated that in humans certain factors such as early menarche, late pregnancy, and nulliparity are associated with a higher risk of developing breast cancer, while early pregnancy acts as a protective factor. Induction of mammary cancer in rats by administration of the chemical carcinogen 7,12-dimethylbenz(a)anthracene reveals that the same factors influencing human breast cancer risk also affect the susceptibility of the rat mammary gland to the chemical carcinogen. Nulliparous rats and rats undergoing pregnancy interruption are more susceptible to developing carcinomas. This fact has been attributed to the incomplete differentiation of the gland at the time of carcinogen administration. Parous rats are resistant to the carcinogenic effect of DMBA, which is explained by the complete development of the gland attained during pregnancy and lactation. This development is manifested by the differentiation of terminal end buds into secretory units, which have a smaller proliferative compartment; the epithelial cells of these secretory units have a longer cell cycle, less avidity for binding DMBA, and possess a more efficient DNA excision repair capacity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Changes in the serum of mice infected with Streptococcus pneumoniae that stimulate in-vitro multiplication of virulent but not avirulent strains.

During pneumococcal infection of mice, nucleic-acid products, including deoxynucleotides, may be released into the serum from cellular disintegration in at least three organs, the lungs, spleen and liver. The serum, after sterilisation to remove contaminating pneumococci, stimulated multiplication of virulent but not avirulent pneumococci in vitro. It also stimulated growth of virulent pneumococci in serum from uninfected animals and could be replaced, at least in part, by certain nucleic-acid degradation products at concentrations found in infected serum. The effects of the serum were lost after dialysis or dilution.

Animals↗
PubMed1982

Piperacillin distribution into bile, gallbladder wall, abdominal skeletal muscle, and adipose tissue in surgical patients.

The concentrations of piperacillin in serum, bile, gallbladder wall, abdominal skeletal muscle, and adipose tissue were measured simultaneously at various times after the intravenous administration of a single 5-g dose to each of 14 patients undergoing biliary tract surgery. Piperacillin concentrated in the bile with peak levels exceeding 4,000 micrograms/ml. In a single patient with cystic duct obstruction, trace gallbladder bile piperacillin levels were measured. Gallbladder wall concentrations of piperacillin tended to be higher than corresponding serum concentrations, with a correlation observed between tissue values and the degree of acute gallbladder inflammation and gallbladder bile piperacillin concentrations. Mean peak muscle and adipose tissue piperacillin concentrations of 31 and 27 micrograms/g, respectively, were reached at between 2 and 3 h after the start of infusion. These concentrations exceeded the minimum inhibitory concentration for a majority of susceptible organisms. A single 5-g dose of piperacillin achieved therapeutic levels in gallbladder wall, intraabdominal skeletal muscle, and adipose tissue and concentrated in the bile of patients with patent biliary tracts.

Abdominal Muscles↗
PubMed1982

Endocrinologic milieu and susceptibility of the rat mammary gland to carcinogenesis.

The incidence of DMBA-induced mammary carcinomas in Sprague-Dawley rats depends upon their previous reproductive histories. Young virgin rats (YV) are highly susceptible to the carcinogen, while old virgin rats (OV) are less susceptible, and parous rats (P) are resistant. The authors performed endocrinologic studies in these three groups of rats in order to determine whether the different susceptibility to carcinogenesis, according to the reproductive history, is or is not related to the hormonal milieu. The pituitary, the ovaries, the adrenals, and the mammary glands were processed for light microscopy. Pituitary prolactin (PRL), follicle-stimulating hormone, and luteinizing hormone cells were immunostained by peroxidase-antiperoxidase and quantitated with an image analyzer. Radioimmunoassays of serum and pituitary PRL and serum estradiol were also done. The results showed no differences in the hormonal milieu of YV, OV, and P rats at the time of carcinogen treatment. Several changes were observed after DMBA administration, the most conspicuous being 1) hyperplasia of pituitary PRL cells, 2) high serum PRL levels, 3) nodular hyperplasia of the adrenal cortex, 4) high serum estradiol levels, and 5) lack of adrenal necrosis in P rats and some OV rats. These modifications did not correlate with the degree of susceptibility of YV, OV, and P rats to carcinogenesis, supporting the concept of the importance of the mammary gland differentiation at the moment of carcinogen administration. (Am J Pathol 1982, 109:47-56).

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

Influence of age and parity on the susceptibility of rat mammary gland epithelial cells in primary cultures to 7,12-dimethylbenz(a)anthracene.

Mammary gland epithelial cells from rats of different ages or with different reproductive histories vary in their proliferative properties and susceptibility to dimethylbenz(a)anthracene (DMBA) carcinogenesis in vivo. The present study was carried out to determine whether these differences are maintained under in vitro conditions. Primary cultures of mammary gland epithelial cells of young virgin, old virgin, and parous rats were treated with various doses of DMBA. Growth rates, DNA synthesis, and dose-response curves were determined; the toxicity of DMBA was measured by its effect on cell growth. Cell morphology was studied by transmission and scanning electron microscopy. Epithelial cells from the mammary gland of young virgin rats adapted rapidly to the culture conditions, behaving as if the cells were in the logarithmic phase of growth prior to plating. Mammary gland epithelial cells from old virgin and parous rats required a lag period prior to cell growth during which the proliferating cells adapted to the culture conditions. Cells from each group had comparable doubling times, and DNA synthesis peaked approximately 1 d after initiation of growth in culture. The numbers of proliferating cells decreased with increasing age and parity of the donor. Mammary gland epithelial cells of young virgin rats were more susceptible to both low and high doses of DMBA than those of old virgin and parous rats when the carcinogen was added either 24 h after plating or at the peak of DNA synthesis. These results indicate that age and parity influence the proliferative status of the cells and their susceptibility to DMBA in vitro, simulating in that way the in vivo situation.

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

Epithelial characteristics of five subpopulations of a heterogeneous strain BALB/cfC3H mouse mammary tumor.

We have described previously the isolation and characterization of five distinct subpopulations of tumor cells from a single spontaneous strain BALB/cfC3H mouse mammary tumor (Cancer Res., 38: 3174--3181, 3758--3763, 1978). Subpopulations 68H and 4.10 are polygonal and grow in epithelioid patterns in vitro, whereas subpopulations 66, 67, and 168 are fusiform and grow in lattice or fibroblast-like patterns. Line 4.10 produces tumors with distinctly glandular architecture, whereas the other four subpopulations produce poorly differentiated tumors with mixed epithelial-sarcomatous histological patterns. All five lines were evaluated for epithelial characteristics. Dome formation, characteristic of transporting epithelial cells, could be induced by dexamethasone or dimethyl sulfoxide only in line 4.10 cells. Antibodies to cell type-specific mammary epithelial antigens reacted with each of the subpopulations. All five subpopulations had ultrastructural features of epithelial cells, including desmosomes (all five lines), junctional complexes (68H, 4.10, early-passage 66 and 67 only; poorly defined in 168), and growth in cords demonstrating polarity (68H cells). Less definitive myoepithelial characteristics were also seen in four of the lines, including an incomplete reaction for Na+-K+-ATPase (4.10 cells), hemidesmosome-like junctions (168 and early-passage 66 cells), and pinocytotic vesicles at lower than normal frequency (66, 67, and 168 cells). Thus, none of the lines were distinctly myoepithelial. We conclude that the five subpopulations are epithelial cells that express a spectrum of epithelial characteristics.

Animals↗
PubMed1981

7,12-dimethylbenz[a]anthracene-induced DNA binding and repair synthesis in susceptible and nonsusceptible mammary epithelial cells in culture.

The effect of age and parity on the binding of 7,12-dimethybenz[a]anthracene (DMBA) to DNA and the repair of DMBA-damaged DNA have been demonstrated in logarithmic phase and confluent mammary epithelial cell cultures from young virgin (YV), old virgin (OV), and parous (P) noninbred and inbred Sprague-Dawley rats. Over a dose range of 0.1-0.4 micrograms DMBA/ml, DNA binding was 1.5-to 2.0-fold higher in YV cells than in OV or P cells. In addition, a steeper slope of the dose-response curve was obtained with YV cells, suggesting a greater susceptibility of YV cells to DMBA. Excision repair was determined by measuring, in the presence of hydroxyurea and 5-bromodeoxyuridine, tritiated thymidine incorporation into DNA during the repair process. At high doses od DMBA (0.5-2.0 micrograms/ml), excision repair in YV cells was 1.5 times higher than in OV cells and 2 times higher than in P cells. However, with lower DMBA doses (less than 0.5 micrograms/ml) similar levels of repair were obtained in all 3 groups of rats. Since binding to DNA is higher in YV cells at these low DMBA doses, ti is apparent that OV and P cells exhibit a greater DNA repair per unit damage. These results, therefore, suggest that age and parity not only lower the binding of DMBA to mammary epithelial cell DNA but also increase the efficiency of DNA repair processes, which may explain the lower susceptibility of OV and P rats to DMBA-induced mammary carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Susceptibility of the mammary gland to carcinogenesis. II. Pregnancy interruption as a risk factor in tumor incidence.

In the rat, pregnancy and lactation prior to carcinogen administration protect the mammary gland from developing carcinomas and benign lesions. In this study, the influence of pregnancy interruption versus full pregnancy and pregnancy plus lactation on the incidence of carcinomas and benign lesions was studied in the mammary glands of rats treated with 7,12-dimethylbenz(a)anthracene (DMBA). Fifty-nine Sprague-Dawley rats were separated into 5 groups: I) rats that had had one pregnancy and one lactation; II) rats that had had one pregnancy without lactation; III) rats that had had pregnancy interrupted at the 12th day of gestation; IV) age-matched virgin rats as a control Group I; and V) age-matched virgin rats as a control for groups II and III. The 5 groups received a single intragastric dose of DMBA (10 mg/100 g body weight), with the exception of 2 animals per group, which were killed 1 hour after an intraperitoneal injection of 2.5 mu Ci 3H-thymidine/g body weight. The number of labeled nuclei per 100 cells (DNA labeling index, LI) was counted in terminal end buds (TEBs), terminal ducts (TDs), and alveolar buds (ABs) of the glands. The number of structures and the DNA-LI were correlated with the incidence of tumors at 22 weeks after DMBA. Pregnancy, with or without lactation, resulted in elimination of TEBs and reduction in the DNA-LI of TDs and ABs. These groups did not develop carcinomas. After the interruption of pregnancy the mammary gland contained numerous TEBs, with a high DNA-LI; 77% of these animals developed carcinomas, and all of them developed benign lesions. Therefore, while pregnancy and lactation protected the mammary gland from developing carcinomas and benign lesions by induction of full differentiation, pregnancy interruption did not elicit sufficient differentiation in the gland to be protective, and these animals were at the same risk as virgin animals treated with the carcinogen.

9,10-Dimethyl-1,2-benzanthracene↗