Jorge Blanco

Document Type

Thesis

Date of Award

5-2008

School/College

College of Science, Engineering, and Technology (COSET)

Degree Name

MS in Biology

First Advisor

Desiree Jackson

Abstract

Arsenic is an element found naturally in ground water. Arsenic is detrimental to health and has been linked to various diseases including, skin lesions, Blackfoot disease, and cancer of the bladder, kidney, lungs, skin, and prostate. Areas with high levels arsenic exposure through drinking water have been seen to have an increase in the aforementioned diseases. Previous studies have shown arsenic to be a promoter of carcinogenesis. Rats exposed to arsenic have had a 50% accumulation of inorganic arsenic in the lungs within one hour of exposure. Other studies have also shown that arsenic crosses the placenta and affects the developing embryo. This work will show whether certain genes linked to carcinogenesis are affected in fetal rats that have been pre- and peri-Nataly exposed to arsenic. The hypothesis of this study is that pre- and peri-natal exposure to arsenic will alter gene expression in genes involved in carcinogenesis. The purpose of this study is to find the changes in gene expression after exposure to arsenic that may lead to tumors and cancer development. 1 2 Timed pregnant female rats were exposed to 200 ppm sodium arsenate via drinking water during the embryonic period (gestational day 7 through gestational day 21). Control animals received untreated water for the same duration. One experimental group, mother and pups, was sacrificed immediately after dams gave birth and the lungs retrieved. A second experimental group was further exposed to 200 ppm sodium arsenate for 10 days post-Nataly, mothers via drinking water, and pups via breast milk. The lungs were retrieved after the 10 day period. Harvested adult and fetal lung tissues were frozen in liquid nitrogen and stored at - 40°C. Messenger RNA isolation was completed and analysis of genes related to cell proliferation, PCNA and Cyclin Dl, apoptosis, BAX and BCL-2, and oxidative stress, MnSOD, were performed using Real Time Reverse Transcriptase PCR. Gene expression related to cell proliferation (Cyclin D1 and PCNA) was reduced in the dams in response to direct Arsenic exposure. Arsenic exposure in the pups seems to increase expression of cell proliferation genes. This could be related to the level of exposure that the dams received versus the pups. Reduction of Reactive Oxygen Species associated with oxidative stress "resulting from Arsenic exposure appears to be effective since there were higher levels of expression of - - Manganese Superoxide Dismutase (MnSOD) in the group exposed pre-Nataly versus the group exposed for a longer period. MnSOD was expressed at higher levels in the dams than in the pups. A similar trend of down-regulation in cell proliferation genes was seen in the group exposed for a longer period as seen in the pre-Nataly exposed group. The amount of exposure to the dams could have been great enough to be toxic to the cells thus explaining this reduction. In the pups, the amount of Arsenic could have been reduced, but enough to cause genotoxic effects

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