Metabolic Activation of Sulfur Mustard Leads to Oxygen Free Radical Formation
Abstract
We recently published electron paramagnetic resonance (EPR) spin trapping results that demonstrated the enzymatic reduction of sulfur mustard sulfonium ions to carbon-based free radicals using an in vitro system containing sulfur mustard, cytochrome P450 reductase, NADPH, and the spin trap alpha-(4-pyridyl-1-oxide)-N-tertbutylnitrone (4-POBN) in buffer (A.A. Brimfield et al., 2009, Toxicol. Appl. Pharmacol. 234:128 134). Carbonbased radicals have been shown to reduce molecular oxygen to form superoxide and, subsequently, peroxyl and hydroxyl radicals. In some cases, such as with the herbicide paraquat, a cyclic redox system results, leading to magnified oxygen free radical concentration and sustained tissue damage. Low mustard carbon radical concentrations recorded by EPR in our in vitro system, despite a robust (4.0 mM) sulfur mustard starting concentration, led us to believe a similar oxygen reduction and redox cycling process might be involved with sulfur mustard. A comparison of the rate of mustard radical POBN adduct formation in our in vitro system by EPR at atmospheric and reduced oxygen levels indicated a sixfold increase in 4-POBN adduct formation (0.5 to 3.0 micrometer)
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2012
- Accession Number
- ADA561818
Entities
People
- A. A. Brimfield
- J. S. Graham
- K. A. Trimmer
- M. A. Zottola
- R. E. Sweeney
- S. D. Soni
Organizations
- United States Army Medical Research Institute of Chemical Defense