| 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 | Zdenka Matijasevic, Michael R Volkert
(Affiliation: Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655, United States.)
|
| Journal | DNA repair
(DNA Repair (Amst))
Vol. 6
Issue 6
Pg. 733-41
(Jun 1 2007)
ISSN: 1568-7864 Netherlands |
| PMID | 17292678
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
|
| Chemical References |
- Mustard Gas
- 2-chloroethyl ethyl sulfide
- Luciferases
- DNA Glycosylases
|
| Topics |
- Animals
- Cell Survival
- DNA Damage
- DNA Glycosylases
(metabolism)
- DNA Repair
- Escherichia coli
(metabolism)
- Luciferases
(metabolism)
- Models, Chemical
- Models, Molecular
- Molecular Conformation
- Mustard Gas
(analogs & derivatives, toxicity)
- Mutagenesis
|
