Date of Graduation

Spring 5-2012

Level of Access

Restricted: Campus/Bates Community Only Access

Degree Name

Bachelor of Science

Department or Program

Biological Chemistry

Number of Pages

98

Abstract

Inorganic arsenic is a known carcinogen associated with type II diabetes mellitus. Developmental exposure to arsenic may induce low birth weight and fetal malnutrition, possibly causing diabetes and obesity later in life. More than 13 million Americans are exposed to low concentrations of arsenic (<300 >ppb) through groundwater from wells drilled into arsenic-containing bedrock. Globally, over 100 million people consume arsenic-tainted groundwater at concentrations higher than the EPA and WHO standard of 10 ppb, with the worst cases appearing in Bangladesh and Taiwan. While high dose exposure to arsenic is clearly linked to cancer and diabetes, the role of low dose exposure as a carcinogen and diabetogen is still uncertain. In this thesis, I examined possible genetic and epigenetic mechanisms of toxicity resulting from transplacental arsenic exposure in male mice. I hypothesized that male mice exposed to arsenic early in development would exhibit aberrant expression in genes related to diabetes and liver cancer. I also hypothesized that these changes originated from abnormal epigenetic programming. The gene expression of 384 genes important to diabetes, inflammation, and cancer were examined through quantitative PCR array analysis. Seven genes related to cancer, steroids, or energy metabolism were identified as abnormally expressed potentially due to aberrant epigenetic modifications. I investigated the source of gene repression further by examining global and site-specific methylation patterns in the genomic DNA of arsenic-exposed mice. Overall, this thesis provides further insight into the possible diabetogenic and hepatocarcinogenic mechanisms of low-dose developmental arsenic exposure in mammals.

Components of Thesis

1 pdf file

Restricted

Available to Bates community via local IP address or Bates login.

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