title: Base excision repair sensitizes cells to sulfur mustard and chloroethyl ethyl sulfide.
abstract: DNA repair generally functions to improve survival and reduce mutagenesis of cells that have suffered DNA damage. In this study we examine the role of nucleotide excision repair (NER) and base excision repair (BER) in recovery, mutagenesis and DNA repair in response to DNA damage inflicted by the mustard compounds, sulfur mustard (SM) and chloroethyl ethyl sulfide (CEES) in bacteria and mammalian cells. SM and CEES are compared because SM produces cross-links and monoadducts, whereas CEES produces only monoadducts that are similar to those produced by SM, thus allowing the examination of which types of lesions may be responsible for the effects seen. We find that the presence of a functional NER pathway increases survival and reduces mutagenesis, whereas the presence of a functional BER pathway reduces survival, increases mutagenesis, and decreases repair. The deleterious effects of BER appear to be due to an interaction between the DNA glycosylases and the lesions produced by SM and CEES. Possible mechanisms for BER-mediated sensitization by glycosylase action on mustard lesions are discussed.
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655, United States.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Matijasevic
authors.forename: Michael R
authors.initials: MR
authors.lastname: Volkert
mesh_terms: D000818:Animals; D002470:Cell Survival; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D004926:Escherichia coli / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000633:toxicity*; D016296:Mutagenesis
chemical_list: C031278:2-chloroethyl ethyl sulfide; D008156:Luciferases; D045647:DNA Glycosylases; D009151:Mustard Gas