Protection against the Acute and Delayed Toxicity of Mustards and Mustard-Like Compounds.
Abstract
The toxicity of sulfur mustards is evidently related to the damage they inflict on cellular DNA. Previous studies have shown that much of the acute toxicity of bifunctional mustards can be attributed to DNA cross-linking through two guanine moieties in opposite DNA strands. Analysis of the mutagenic effects of these compounds has indicated that delayed toxicity, on the other hand, may be caused by substitution in the 6 position of guanine and perhaps by other minor DNA modifications as well. However, previous studies have failed to provide chemical evidence for reaction of the sulfur mustards with the 6 position of guanine. We have reexamined this problem using high pressure liquid chromatography to separate the products of the reaction between chloroethyl ethyl sulfide (CEES) and deoxyguanosine. Using this technology, we have shown conclusively that CEES does react with the 6 position of guanine to produce 0(6)-ethylthioethyl deoxyguanosine, thereby providing a firm basis for the suggestion that this lesion could be responsible for the delayed toxicities of sulfur mustards.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1983
- Accession Number
- ADA146943
Entities
People
- D. B. Ludlum
Organizations
- Albany Medical College