Accession Number : ADA583962


Title :   Assessing Protection Against OP Pesticides and Nerve Agents Provided by Wild-Type HuPON1 Purified from Trichoplusia ni Larvae or Induced via Adenoviral Infection


Descriptive Note : Journal article


Corporate Author : ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD


Personal Author(s) : Hodgins, Sean M ; Kasten, Shane A ; Harrison, Joshua ; Otto, Tamara C ; Oliver, Zeke P ; Rezk, Peter ; Reeves, Tony E ; Chilukuri, Nageswararao ; Cerasoli, Douglas M


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a583962.pdf


Report Date : Jan 2013


Pagination or Media Count : 5


Abstract : Human paraoxonase-1 (HuPON1) has been proposed as a catalytic bioscavenger of organophosphorus (OP) pesticides and nerve agents. We assessed the potential of this enzyme to protect against OP poisoning using two different paradigms. First, recombinant HuPON1 purified from cabbage loopers (iPON1; Trichoplusia ni) was administered to guinea pigs, followed by exposure to at least 2 times the median lethal dose (LD50) of the OP nerve agents tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF), or chlorpyrifos oxon, the toxic metabolite of the OP pesticide chlorpyrifos. In the second model, mice were infected with an adenovirus that induced expression of HuPON1 and then exposed to sequential doses of GD, VX, or (as reported previously) diazoxon, the toxic metabolite of the OP pesticide diazinon. In both animal models, the exogenously added HuPON1 protected animals against otherwise lethal doses of the OP pesticides but not against the nerve agents. Together, the results support prior modeling and in vitro activity data which suggest that wild-type HuPON1 does not have sufficient catalytic activity to provide in vivo protection against nerve agents.


Descriptors :   *ORGANOPHOSPHATES , *PESTICIDES , ADENOVIRUSES , GUINEA PIGS , IN VIVO ANALYSIS , LARVAE , LETHAL DOSAGE , METABOLITES , MICE , NERVE AGENTS


Subject Categories : Agricultural Chemistry
      Organic Chemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE