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.
A...
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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.
In 1896 the scientist Beatson reported that the removal of the ovaries resulted in the reduction of breast cancer tumours (Russo and Irma 1998). Breast cancer is a malignant, metastasizing cancer of the mammary gland. It is the leading cause of death in woman between the ages of 35 - 45. Breast cancer can also occur in males, although less frequent, around 400 men die each year from breast cancer in the united states. (Martini, F., 2004). Studies on rats have shown considerable evidence that rat oestrogens are mammary carcinogens. Oestrogens have shown to stimulate the hormone prolactin. Through studies involving the use of antioestrogens, for example, tamoxifen, "Tamoxifen alone or in combination with the retina all trans-N-(4 hydroxyphenyl)-retinamide (4-HPR) reduces the incidence of NMU-induced mammary tumours in Sprague-Dawley rats." (Jane M. Ussher Ph.D. 1996). This suggests that Oestrogens and Prolactin's can have the effect of the development of breast cancer since the pathogenesis of spontaneous breast cancer in humans is similar to that of chemical-induced rodent mammary cancer. (Jane M. Ussher
Acid rain has been proven to have damage forests, fresh waters and soils, killing insect and aquatic life-forms. It also causes damage to buildings and impacts on human health. Many people do not know what acid rain actually is. Acid rain is any form of precipitation that is unusually acidic, low pH levels, higher than normal amounts of sulfuric and nitric acid, occurs naturally and from man made sources. Forms when gases react in the atmosphere with water, oxygen, and other chemicals (what is acid rain?). The only water that will not have some amount of acidity is pure water. Pure water has a pH of 7 which is neutral; regular, unpolluted rain water has a pH of around 5.6. The acidity in rain water comes from the presence of Carbon Dioxide, Nitrogen Oxide, and Sulfur Dioxide. CO2 reacts with water to form carbonic acid. Nitrogen and water react during lightning storms, forming Nitric Oxide. NO is then oxidized to form N02. The NO2 reacts with water to form nitric acid. Due to this, the pH is lowered to be slightly acidic (Acid Rain). Acid rain can occur naturally in the environment, but the problem occurs when human interaction is the cause of the acidic levels.
Chemical pollution into the environment can cause both genotypic and phenotypic changes in many organisms, including humans. More specifically, environmental pollutants like BPA can act as xenoestrogens (estrogen imitators), ultimately affecting hormonal activity and production in an organism. This alteration in activity and production can be termed as endocrine disruption. The endocrine system regulates a variety of processes responsible for growth and development, including gonadal formation and function, digestion, metabolism, sex differentiation, and embryonic development (reviewed by Flint et al., 2012). Chemicals that interfere with the function or structure of the endocrine system can be defined as endocrine disrupting compounds (EDCs) (US Environmental Protection Agency, 2007).
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.
What would you give to rid yourself of acne? What would you do? The bane of every adolescent’s existence, these red spots develop to some degree in 85% of the population between ages 12 and 25 (Lamberg). Teenagers wake up every morning, look at the mirror, and sigh at the acne on their faces and often other places on their bodies. They dread these awful things that are absolutely ugly. They get desperate and eventually, if the acne grows worse than ever before, they resort to Accutane. Accutane, also known as isotretinoin, is a medication for acne. However, despite isotretinoin’s helpfulness in controlling acne that is unresponsive to other treatments, this medication should not be used because of its harmful physical side effects, its association with psychiatric adverse effects, and its effects on reproduction.
Forensic toxicology is one of the oldest disciplines in forensic science history and dates back hundreds of years. However, the actual understanding and examination of forensic toxicology only dates back for about 200 years. Due to the development of technology, this discipline has been able to progress and flourish.
During recent years, numerous newspaper and magazine articles have suggested that humans may be at risk because small amounts of well known environmental contaminants, such as dioxin, PCBs and DDT, can affect hormone levels. Hormones are produced by the endocrine system as regulators of biological function in target organs. Because hormones play a critical role in early development, toxicological effects on the endocrine system often have an impact on the reproductive system. The term endocrine disruptor is used to describe chemicals that can mimic hormones and may either enhance or counteract their effects. It has been suggested that these hormone changes can, in turn, lead to a variety of health problems including cancer, decreased fertility, and abnormalities in newborns.
Your chance of getting cancer from exposure to a chemical, however, like your chance of being killed in a vehicle accident, is not as easy to understand. This is because conditions that affect your chance are always changing. In the case of a vehicle accident, the road may be slippery, you or another driver may be drunk, your car or another vehicle may get a blow out at high speed, someone may fall asleep at the wheel, someone may throw a rock from an overpass, or an airplane may fall from the sky. All of these conditions and many more affect the chance of being involved in an accident. Sometimes you can control the conditions effectively, but most of the time you can't.
Ninety percent of deaths from tumor are due to metastasis making the pathophysiology of this process and study of genes involved regulating metastasis central to understand the mechanism of this disease (Boimel et al., 2011). Breast cancer seems to originate from changes in the architectural breast tissue organization consequent to interaction between cell genome and extracellular environment. Thus basic cellular processes and their molecular regulation play an important role on the onset of breast cancer. Various transcription factors are involved in regulation and expression of specific genes crucial for cellular mechanism; any alteration in these mechanisms may give rise to series of malignancies including breast cancer (Cantilte et al.,
Asthma is a disease that currently has no cure and can only be controlled and managed through different treatment methods. If asthma is treated well it can prevent the flare up of symptoms such as coughing, diminish the dependence on quick relief medication, and help to minimize asthma attacks. One of the key factors to successful treatment of asthma is the creation of an asthma action plan with the help of a doctor that outlines medications and other tasks to help control the patient’s asthma ("How Is Asthma Treated and Controlled?"). The amount of treatment changes based on the severity of the asthma when it is first diagnosed and may be the dosage may be increased or decreased depending on how under control the patient’s asthma is. One of the main ways that asthma can be controlled is by becoming aware of the things that trigger attacks. For instance staying away from allergens such as pollen, animal fur, and air pollution can help minimize and manage the symptoms associated with asthma. Also if it is not possible to avoid the allergens that cause a patient’s asthma to flare up, they may need to see an allergist. These health professionals can help diagnosis what may need to be done in other forms of treatment such as allergy shots that can help decrease the severity of the asthma ("How Is Asthma Treated and Controlled?").
Panno, Joseph. Cancer: The Role of Genes, Lifestyle, and Environment. New York: Facts On File, 2005. Print.