Naked DNA prevents soman intoxication.
Paraoxonase (Q isoenzyme, PON1) can effectively hydrolyze chlorpyrifos-oxon (CPO), soman, sarin, and other organophosphates. Previous studies had indicated that the levels of serum PON1 in gene therapy with adenoviral vector could decrease the toxicity of CPO. In our study, plasmid pcDNA/PON1 injected into the tail vein of mice gave excellent expression at 24h after delivery, and PON1 activity decreased gradually along with days. The PON1 activities of mice treated with different doses of the plasmid (150, 300, and 600 microg/mouse) indicated a very good dose-effect relationship. Toxicity study has been performed using one lethal dose of soman (200 microg/kg). The mean death latency of mice pre-treated with 150, 300, 600, and 1200 microg pcDNA/PON1 extended and the mortality decreased vs control mice received the null pcDNA. These results demonstrate that increasing serum PON1 by naked DNA can offer protection toward the acute toxicity of soman.
Fu
Ai Ling
AL
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Bejing 100850, PR China.
Wang
Yu Xia
YX
Sun
Man Ji
MJ
D000818:Animals; D043303:Aryldialkylphosphatase / Q000008:administration & dosage* / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D002801:Cholinesterase Reactivators / Q000008:administration & dosage; D004247:DNA / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D020536:Enzyme Activators; D015316:Genetic Therapy / Q000379:methods*; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D012640:Seizures / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D012999:Soman / Q000506:poisoning*; D016019:Survival Analysis; D014018:Tissue Distribution; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D020536:Enzyme Activators; D004247:DNA; D012999:Soman; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human