Protection Against the Acute and Delayed Toxicities of Sulfur Mustard
Abstract
Both the acute and delayed toxicities of DNA damaging agents represent the outcome of a race between protective and toxic pathways triggered by DNA damage. In order to identify targets for therapeutic intervention and conditions that can modulate the outcome of exposure to sulfur mustard we sought to investigate pathways and early events involved in cellular responses to SM-induced damage. We have identified two levels of cellular responses where proper intervention may minimize toxicity. The first level directly involves the activity of DNA repair enzymes, while the second one is based on the regulation of cell cycle progression. We have discovered that in contrast to the protective effect of nucleotide excision repair, alkyl adenine DNA glycosylase, the first enzyme in the base excision repair pathway, sensitizes cells to SM exposure. We show that hypothermia provides protection against SM toxicity. The results suggest that two mechanisms account for this protection: i) hypothermia counteracts sensitizing effect of DNA glycosylase in SM-exposed cells and ii) hypothermia induces reversible cell cycle arrest providing more time for repair of lesions before the critical cellular events, DNA replication and mitosis, take place.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA418731
Entities
People
- Zdenka Matijasevic
Organizations
- University of Massachusetts