Journal ArticleDOI
7,12-Dimethylbenz[a]anthracene-Induced DNA Binding and Repair Synthesis in Susceptible and Nonsusceptible Mammary Epithelial Cells in Culture
Lee K. Tay,Jose Russo +1 more
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TLDR
The results 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.Abstract:
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.read more
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Journal ArticleDOI
Differentiation of the mammary gland and susceptibility to carcinogenesis
TL;DR: 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 chemicalcar carcinogen.
Book ChapterDOI
Comparative study of human and rat mammary tumorigenesis.
Jose Russo,Barry A. Gusterson,Adrianne E. Rogers,Irma H. Russo,Sefton R. Wellings,Matthew J. Van Zwieten +5 more
TL;DR: Lower risk of breast cancer has been reported in women that have had an early full-term pregnancy and among all of these factors, the development of Breast cancer is influenced by the reproductive history of the individual.
Journal Article
Host Factors Affecting the Growth of Carcinogen-induced Rat Mammary Carcinomas: A Review and Tribute to Charles Brenton Huggins
TL;DR: The carcinogen-induced rat mammary carcinoma model is today the standard laboratory animal model in the study of human breast cancer and has a number of features that make it particularly attractive to the experimental oncologist, e.g., tumor induction ease and reliability.
Journal ArticleDOI
The protective role of pregnancy in breast cancer
TL;DR: Evidence is provided that pregnancy, through the process of cell differentiation, shifts Stem cells 1 to Stem Cells 2 – cells that exhibit a specific genomic signature that could be responsible for the refractoriness of the mammary gland to carcinogenesis.
Journal ArticleDOI
Experimentally induced mammary tumors in rats.
Jose Russo,Irma H. Russo +1 more
TL;DR: Using the DMBA rat mammary model, it is demonstrated that the carcinogen acts on the intermediate cell of the terminal end bud (TEB), and that this structure is the one that evolves to intraductal proliferation, carcinoma in situ, and invasive carcinoma.
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Influence of Differentiation and Cell Kinetics on the Susceptibility of the Rat Mammary Gland to Carcinogenesis
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