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 17β-estradiol (E2, 3 mg, s.c.) for either 7, 15, 120 or 240 days. Animals were sacrificed, 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 E2 exposure. Atypical ductal proliferation and significant reduction in stromal fat were observed following 120 days of E2 exposure. Both in situ and invasive carcinomas were observed in the majority of the mammary glands from rats treated with E2 for 240 days. Palpable breast tumors were observed in 82% of E2-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 E2 for 240 days compared to controls. Furthermore, 8-isoprostane (8-isoPGF2α) 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 E2 for 7, 15, 120 and 240 days and compared to activity levels in age-matched controls. 8-isoPGF2α levels displayed time-dependent increases upon E2 treatment and were significantly higher than control levels at the 15, 120 and 240 day time-points. 8-isoPGF2α levels observed in E2-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 E2-treated rats. Taken together, our data reveal that proliferative changes in the breast tissue of ACI rats are associated with increases in 8-isoPGF2α formation as well as changes in the activities of antioxidant enzymes. These oxidative changes appear to be a function of E2 exposure and occur prior to tumor development.
A recent and major scientific achievement in the field of biotechnology is the discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). CRISPR has become one of the most modern and popular tools, mainly due to its low cost and efficiency, which could be used to edit the genome. As a result, this technology holds key to almost every dimension of biomedical and agricultural sciences, and has potential applications in the treatment of viral infections, hemophilia, cancer and inherited genetic anomalies. However, ethical issues could crop up when this technology for editing genes could be unfairly used to improve biological features, solely for the purpose of aesthetics or to gain advantage over others in the population. This would not only lead to societal discrimination and unrest, but also have the potential to change the course of evolution in living beings. In this regard, regulated implementation of the CRISPR technology, risk assessment, policies and procedures should be in place to prevent gross misuse of this technology.
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