Date of Award

8-2004

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. David Reinhold

Second Advisor

Dr. Bruce Bejcek

Third Advisor

Dr. Bryan Tripp

Access Setting

Masters Thesis-Open Access

Abstract

Environmental agents can cause an increase in cellular stress and damage DNA which can lead to diseases such as cancer. Chromium produces cellular stress by increasing the reactive oxygen species through a Fenton-like reaction, where chromium reacts with hydrogen peroxide to form hydroxyl radicals. Benzo[ a ]pyrene is an environmental carcinogen that is metabolized by cytochrome p450 enzymes into benzo[a]pyrene diolepoxide (BPDE). BPDE is highly reactive with DNA producing large DNA-adducts primarily on guanine nucleotides. The primary intracellular pathway by which mammalian cells remove damaged DNA caused by bulky mutagens is nucleotide excision repair. We have found that, in BPDE treated cells the addition of chromium significantly decreases the frequency of mutations in the hypoxanthine phosphoribosyltransferase (HPRT) gene. Using a 32P-postlabeling system it was found that the antagonistic decrease in mutant frequency was due to a significant decrease in the number of adducts produced by BPDE. Using cell lines deficient in various DNA repair mechanisms, it was discovered that this reduction may involve an increase in global genomic repair, which is a sub-pathway of nucleotide excision repair. The way in which chromium elicits this increase of repair is not yet characterized, but it appears to be independent of the p53 protein.

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