Date of Award
Level of Access Assigned by Author
Doctor of Philosophy (PhD)
Biochemistry and Molecular Biology
John Pierse Wise, Sr
Second Committee Member
Third Committee Member
Amy J Davidoff
Hexavalent chromium (Cr(VI)) is a well-established human lung carcinogen. Solubility plays a crucial role in Cr(VI)-induced carcinogenesis, with the particulate form being the most potent. However, the carcinogenic mechanisms of particulate Cr(VI) compounds are uncertain. Cell transformation studies show that defective repair of DNA double strand breaks is required for the carcinogenicity of Cr(VI) after prolonged exposure. Therefore, our study investigates the effects of prolonged exposure to particulate Cr(VI) on the formation of DNA double strand breaks and repair. We found that prolonged exposure to particulate Cr(VI) induced persistent levels of DNA double strand breaks and chromosome aberrations. In order to differentiate the different kinetics of breaks and determine the fate of cells, we investigated the formation of DNA double strand breaks in live cells. We observed fast and slow resolving foci indicating that cells exhibited different repair capacity after shorter exposures. We also observed cells with slow resolving foci undergoing normal cell division indicating damaged cells have the potential to divide and the DNA damage is heritable. Lastly, we assessed the two major repair mechanisms of DNA double strand breaks. We found that short exposure to particulate Cr(VI) activated homologous recombination repair signaling, an error-free repair mechanism, while prolonged exposure to particulate Cr(VI) activated non- homologous end joining repair signaling, an error-prone repair mechanism. The repair signaling of Cr(VI)-induced DNA double strand breaks switched from homologous recombination to non-homologous end joining, which potentially promotes Cr(VI)- induced carcinogenesis.
Qin, Qin, "Characterizing the Impact of Prolonged Exposure to Particulate Hexavalent Chromium on DNA Double Strand Break Repair" (2013). Electronic Theses and Dissertations. 1952.