title: Mustard gas surrogate, 2-chloroethyl ethylsulfide (2-CEES), induces centrosome amplification and aneuploidy in human and mouse cells : 2-CEES induces centrosome amplification and chromosome instability.
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 unstable governments. Mustard gas is a powerful vesicant and alkylating agent that causes painful blisters on epithelial surfaces and increases the incidence of cancer in those exposed. 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. Interestingly, several proteins that have been shown to either be targets of mustard gas or mediate mustard gas toxicity have also been shown to regulate centrosome duplication. Centrosomes are small nonmembrane-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 during mitosis 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, induce centrosome amplification and chromosome instability in cells, which may hasten the mutation rate necessary for tumorigenesis. These data may explain why those exposed to mustard gas exhibit higher incidences of cancer than unexposed individuals of the same cohort.
authors.affiliation: Biology Department, University of Southern Indiana, Evansville, IN, 47712, USA, rabennett@usi.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bennett
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Behrens
authors.forename: Ashtyn
authors.initials: A
authors.lastname: Zinn
authors.forename: Christian
authors.initials: C
authors.lastname: Duncheon
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lamkin
mesh_terms: D000782:Aneuploidy; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018385:Centrosome / Q000187:drug effects* / Q000502:physiology; D002619:Chemical Warfare Agents / Q000633:toxicity*; D043171:Chromosomal Instability; D006801:Humans; D051379:Mice; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000633:toxicity; D041681:NIH 3T3 Cells
chemical_list: D002619:Chemical Warfare Agents; C031278:2-chloroethyl ethyl sulfide; D009151:Mustard Gas