Investigating the Effects of Arsenic Exposure on Gene Expression in Breast Cancer Cells
A) SPECIFIC AIMS
Breast cancer is the second leading cancer to cause death in women. A combination of factors contributes to the etiology of breast cancer, such as genetic and environmental dynamics [ACS, 2014]. One particular area of interest is the study of metalloestrogens, which are inorganic compounds that can bind to the estrogen receptor and mimic the biological functions of estrogen in breast cancer cells. Arsenic is one such metalloestrogen and has been classified as carcinogenic to humans [IARC]. Studies in humans have shown that long-term exposure to arsenic is associated with bladder, kidney, lung and liver cancers [1,2,3]. Arsenic exposure has also been correlated with an increase in the incidence of breast cancer [4]. People can be exposed to arsenic in different settings such as in the workplace, in drinking water or from medical treatments. Through these methods of exposure, various mechanisms of internalization can take place through inhalation, ingestion, or through skin contact. We hypothesize that prolonged arsenic exposure results in the expression of genes that promote breast cancer progression. In this study, we propose to investigate the effect of prolonged arsenic exposure on gene expression, by comparing the global gene expression of a breast cancer cell line that has been chronically exposed to low-dose arsenic with that of a control cell line. Genes found to be differentially expressed in arsenic adapted cells will be examined further. We also aim to extend our understanding of the direct effect of arsenic, by studying the signal pathway that results in gene expression when arsenic binds to the estrogen receptor.
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...rns associated with estrogen expression in different experimental conditions.
The proposed research will identify gene expression traits of breast cancer cells chronically exposed to arsenic during different periods of exposure. These results will allow us to develop gene profiles and identify arsenic-associated genes. By identifying arsenic-associated genes, we can determine if these genes are involved in molecular functions and biological processes. This study can assist future studies of mammary tumors with elevated arsenic levels and will provide insight into breast cancer progression due to the accumulation of arsenic. Our proposed research will demonstrate the impact of arsenic on the estrogen receptor and on breast cancer carcinogenesis. We hope this study will highlight the importance of studying the effects of prolonged arsenic exposure on breast cancer.
Two case-control 4,5, two nested case-control2,6 and two cohort1,7 studies reported estimates for the association between Tetrachloroethylene (TCE) exposure and primary liver cancer. A non-significant association was found between occupational solvent exposure and primary liver cancer among one case-control study, while the other observed a significant association. Hemberg et al. found the odds ratio (OR) for heavy/moderate exposure compared with little/no exposure was 2.3 (95% CI: 0.8, 7.0). The association was confined to women (exact Fisher’s chi-square p=0.007) with the men having a non-significant odds ratio of 0.5. Stemhagen et al. found that among men, the OR for working laundry or dry cleaning compared to not working in that occupation was 2.50 (95% CI: 1.02,...
The health effects that exposure of inorganic arsenic are such as isolation on the stomach, and intestines, also causes decreased production of red and white blood cells, skin changes, and lug irritation. Is also suggested that taking amounts of arsenic can intensify the chances of developing cancer, especially in the skin, lung, liver, and lymph. In woman arsenic can cause infertility and abortion. Another effects that it can cause are damage in the DNA, disruption of the skin, disturbance in the heart, and brain damage in both, men and women.
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Arsenic is the 20th most common element in the earth’s crust and can be found naturally in our environment. There is around 0.006 to 0.03 ppm or arsenic distributed in seawater, and 20 ppm of arsenic in soil (before pesticides). Every human will ingest about 0.5 to 1 mg of arsenic in a day from food and water, because arsenic is present in higher quantities in se...
... in inhabitants living close to smelters and arsenical chemical factories. Citizens who live near waste sites with arsenic may have an increased risk of lung cancer as well.
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