Multiple Animal Studies for Medical Chemical Defense Program in Soldier/ Patient Decontamination and Drug Development
Abstract
Exposure to sulfur mustard (HD) may introduce cross-linkages and breaks into DNA strands, which if not repaired, can results in cell death. Hypothetically, excessive activation of the DNA repair enzyme, poly(ADP-ribose) polymerase, following HD exposure results in the depletion of oxidized nicotinamide adenine dinucleotide (NAD+), a cofactor essential for maintaining cellular viability. To test this hypothesis, the influence of three poly(ADP- ribose) enzyme inhibitors; 3-aminobenzamide (3AB), nicotinamide (NIC), and nicotinic acid (NA) was examined on the lethality and hematologic effects of subcutaneously administered HD using male, CD-1 mice. Two subcutaneous HD challenge doses approximating either the LD30 (22.0 mg/kg) or LD60 (28.2 mg/kg) were administered to groups of mice receiving intraperitoneal doses of each enzyme inhibitor. Three different inhibitor dose levels were tested at different administration time combinations relative to the HD challenge. Only 3 AB exhibited a significant (P < 0.05) effect in lowering HD mortality. This effect did not, however, appear to be dose-dependent over the range tested and appeared to be dependent on the time of administration.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1988
- Accession Number
- ADB129563
Entities
People
- Paul I. Feder
- Ronald L. Joiner
- Thomas H. Snider
- W. B. Keys Jr.
Organizations
- Battelle Memorial Institute