Protection Against the Acute and Delayed Toxicities of Sulfur Mustard
Abstract
Our investigations of the mechanisms of sulfur mustard (SM) toxicity and conditions that can improve cell survival after exposure have previously demonstrated that cells with compromised nucleotide excision repair (NER) are very sensitive to SM. In vitro experiments implicated base excision repair (BER) as another pathway involved in the processing of SM-damaged DNA. We find that the DNA glycosylase that initiates BER, sensitizes cells to SM, probably due to formation of repair intermediates more toxic than the initial lesion. This represents a novel lead in the search for modulators of SM toxicity. Once we establish the mechanism of sensitization, we will pursue investigation directed toward the inhibitors of the glycosylase, and/or activators of alternative repair pathways. We have demonstrated that hypothermia can ameliorate the sensitizing effects of glycosylase activity. In addition, hypothermia also has a glycosylase-independent beneficial effect on cell survival. Our data indicate that p53-mediated cell cycle arrest induced by low temperature may account for the additional protection by hypothermia.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2002
- Accession Number
- ADA408174
Entities
People
- Zdenka Matijasevic
Organizations
- University of Massachusetts