Estrogen-induced breast cancer: Alterations in breast morphology and oxidative stress as a function of estrogen exposure
- Department of Environmental Health Science Mailman School of Public Health Columbia University 60 Haven Avenue, B106, New York, NY 10032 (United States)
- Department of Pathology, Columbia University Medical Center, New York, NY 10032 (United States)
- Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)
Epidemiological evidence indicates that prolonged lifetime exposure to estrogen is associated with elevated breast cancer risk in women. Oxidative stress and estrogen receptor-associated proliferative changes are suggested to play important roles in estrogen-induced breast carcinogenesis. In the present study, we investigated changes in breast morphology and oxidative stress following estrogen exposure. Female ACI rats were treated with 17{beta}-estradiol (E{sub 2}, 3 mg, s.c.) for either 7, 15, 120 or 240 days. Animals were euthanized, tissues were excised, and portions of the tissues were either fixed in 10% buffered formalin or snap-frozen in liquid nitrogen. Paraffin-embedded tissues were examined for histopathologic changes. Proliferative changes appeared in the breast after 7 days of E{sub 2} exposure. Atypical ductal proliferation and significant reduction in stromal fat were observed following 120 days of E{sub 2} exposure. Both in situ and invasive carcinomas were observed in the majority of the mammary glands from rats treated with E{sub 2} for 240 days. Palpable breast tumors were observed in 82% of E{sub 2}-treated rats after 228 days, with the first palpable tumor appearing after 128 days. No morphological changes were observed in the livers, kidneys, lungs or brains of rats treated with E{sub 2} for 240 days compared to controls. Furthermore, 8-isoprostane (8-isoPGF{sub 2{alpha}}) levels as well as the activities of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase and catalase, were quantified in the breast tissues of rats treated with E{sub 2} for 7, 15, 120 and 240 days and compared to activity levels in age-matched controls. 8-isoPGF{sub 2{alpha}} levels displayed time-dependent increases upon E{sub 2} treatment and were significantly higher than control levels at the 15, 120 and 240 day time-points. 8-isoPGF{sub 2{alpha}} observed in E{sub 2}-induced mammary tumors were significantly higher than levels found in control mammary tissue from age-matched animals. Similarly, alterations in glutathione peroxidase and superoxide dismutase activities were detected in both mammary and tumor tissue from E{sub 2}-treated rats. Taken together, our data reveal that proliferative changes in the breast tissue of ACI rats are associated with increases in 8-isoPGF{sub 2{alpha}} formation as well as changes in the activities of antioxidant enzymes. These oxidative changes appear to be a function of E{sub 2} exposure and occur prior to tumor development.
- OSTI ID:
- 21144123
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 232, Issue 1; Other Information: DOI: 10.1016/j.taap.2008.06.007; PII: S0041-008X(08)00250-0; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Synthesis and biological evaluation of fluorine-18-labeled estrogens and progestins as positron emission tomography (PET) imaging agents
Synergism of estrogens and X-rays in mammary carcinogenesis in female ACI rats