Sister Chromatid Exchange Assay of Physostigmine Salicylate in Chinese Hamster Ovary Cells

摘要

Soman, the primary nerve agent utilized by threat forces , is refractory to the standard antidotal therapy, atropine and 2-PAM chloride, fielded by the U.S. Army. Consequently, the highest priority has been placed on fielding a more effective treatment regimen. A regimen incorporating a carbamate, pyridostigmine, as a prophylactic agent, combined with standard atropine/2-PAM chloride therapy, has proven extremely effective in reducing mortality in Rhesus monkeys exposed to multilethal concentrations of soman (1). However, the animals require a prolonged period of recovery during which they are completely incapacitated. Consequently, a tertiary carbamate, physostigmine, has been proposed as a prophylactic agent since it would protect the central nervous system in addition to the peripheral nervous system. The potential of physostigmine salicylate to induce Sister Chromatid Exchanges (SCEs) was assessed using Chinese Hamster Ovary (CHO) cells. Cells were exposed to doses ranging from 0.5 mg/ml to 0.025 mg/ml in cultures with and without exogenous metabolic activation provided by rat liver S-9. Physostigmine salicylate induced a statistically significant dose dependent increase in SCEs both with and without exogenous metabolic activation. Keywords: Toxicity, DNA damage, Genetic Toxicology, Mutagens. (aw)