Date on Master's Thesis/Doctoral Dissertation

12-2021

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Wise, Sr., John P.

Committee Co-Chair (if applicable)

Wise, Sandra S.

Committee Member

Wise, Sandra S.

Committee Member

Lu, Cai

Committee Member

Hein, David W.

Committee Member

Koukam, Calvin J.

Committee Member

Liu, Ke Jian

Author's Keywords

Hexavalent chromium; carcinogenesis; lung cancer; epithelial cells; chromosome instability; DNA Repair Inhibition

Abstract

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.

Included in

Toxicology Commons

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