Date on Master's Thesis/Doctoral Dissertation

12-2018

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Wise, Sr. John Pierce

Committee Co-Chair (if applicable)

Wise, Sandra S.

Committee Member

Wise, Sandra S.

Committee Member

States, J. Christopher

Committee Member

Beverly, Levi J.

Committee Member

Damodaran, Chendil

Committee Member

Hoyle, Gary

Author's Keywords

chromosome instability; aneuploidy; physeter macrocephalus; balaena mysticetus; zinc chromate

Abstract

Hexavalent chromium [Cr(VI)] is a widespread environmental and occupational carcinogen. The mechanism of carcinogenesis remains poorly understood, but chromosome instability (CIN) is the dominant theory. How numerical CIN arises is unclear, but it correlates with centrosome amplification. Both phenotypes are hallmarks of cancers, early events in carcinogenesis, and have been shown to occur after Cr(VI) exposure to human skin and lung fibroblasts. In this study, we investigate numerical CIN and centrosome amplification in whale cells. Whales are our closest marine relatives, have long lifespans, and are exposed to environmental Cr(VI). Importantly, they have low cancer rates and cell culture studies show they are resistant to Cr(VI) genotoxicity. This study found increasing concentrations and prolonged exposure to zinc chromate produced no increase in aneuploid metaphases or centrosome amplification in interphase or mitotic cells. A concentration-dependent increase in cytotoxicity was measured, but no change in relative survival occurred with prolonged exposure.

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