Mustard Gas Surrogate, 2-Chloroethyl Ethylsulfide (2-CEES), Induces Centrosome Amplification and Aneuploidy in Human and Mouse Cells
Abstract
Mustard gas is a simple molecule with a deadly past. First used as a chemical weapon in World War I, its simple formulation has raised concerns over its use by terrorist organizations and rogue governments. Mustard gas is a powerful vesicant and alkylating agent and confers painful blisters on epithelial surfaces and increases incidence of cancer. The mechanism of mustard gas toxicity and tumorigenesis is not well understood, but is thought to be mediated by its ability to induce oxidative stress and DNA damage. Centrosomes are small, non-membrane bound organelles that direct the segregation of chromosomes during mitosis through the formation of the bipolar mitotic spindle. Cells with more or less than two centrosomes can segregate their chromosomes unequally, resulting in chromosome instability, a common phenotype of cancer cells. In our studies, we show that subtoxic levels of 2-chloroethyl ethylsulfide (2-CEES), a mustard gas analog, also induce centrosome amplification and chromosome instability in cells, which may hasten the mutation rate necessary for tumorigenesis. These studies offer an explanation why those exposed to mustard gas exhibit higher incidences of cancer than unexposed individuals of the same cohort.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2014
- Accession Number
- ADA599885
Entities
People
- Ashtyn Zinn
- Christian Duncheon
- Elizabeth Behrens
- Richard A. Bennett
- Thomas J. Lamkin
Organizations
- Air Force Research Laboratory