Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Pharmacology and Toxicology, MS
Wise, Sr., John P.
Committee Co-Chair (if applicable)
Wise, Sandra S.
Wise, Sandra S.
Hein, David W.
Koukam, Calvin J.
Liu, Ke Jian
Hexavalent chromium; carcinogenesis; lung cancer; epithelial cells; chromosome instability; DNA Repair Inhibition
Particulate hexavalent chromium [Cr(VI)] is a well-established human lung carcinogen. RAD51, a key protein in homologous recombination repair pathway, is inhibited after prolonged exposure to Cr(VI), leading to an increase in chromosome instability after prolonged exposures in human lung fibroblasts. chromosome instability is the proposed driver of Cr(VI) carcinogenesis. Since tumors from chromate workers develop from epithelial cells, we sought to translate these findings from human bronchial fibroblasts to human bronchial epithelial cells. We hypothesized Cr(VI) inhibits RAD51 after prolonged exposure leading to an increase in chromosome instability in human bronchial epithelial cells (BEP2D). We characterized the cytotoxicity and measured intracellular Cr ion levels, chromosome instability and RAD51 response. Altogether, the data show, in BEP2D cells, Cr(VI) induces DNA double strand breaks and targets RAD51 leading to an increase in chromosome instability, successfully translating the outcomes seen in human bronchial fibroblasts to human bronchial epithelial cells.
Meaza Isusi, Idoia, "Translating particulate hexavalent chomium-induced chromosome instability, loss of homologous recombination repair and targeting of RAD51 from human lung fibroblasts to human bronchial epithelial cells." (2021). Electronic Theses and Dissertations. Paper 4011.