title: Alterations in gene expression in Caenorhabditis elegans associated with organophosphate pesticide intoxication and recovery.
abstract: BACKGROUND
  The principal toxicity of acute organophosphate (OP) pesticide poisoning is the disruption of neurotransmission through inhibition of acetylcholinesterase (AChE). However, other mechanisms leading to persistent effects and neurodegeneration remain controversial and difficult to detect. Because Caenorhabditis elegans is relatively resistant to OP lethality--particularly through the inhibition of AChE--studies in this nematode provide an opportunity to observe alterations in global gene expression following OP exposure that cannot be readily observed in less resistant organisms.
  
  
  RESULTS
  We exposed cultures of worms in axenic, defined medium to dichlorvos under three exposure protocols. In the first, worms were exposed continuously throughout the experiment. In the second and third, the worms were exposed for either 2 or 8 h, the dichlorvos was washed out of the culture, and the worms were allowed to recover. We then analyzed gene expression using whole genome microarrays from RNA obtained from worms sampled at multiple time points throughout the exposure. The worms showed a time-dependent increase in the expression of genes involved in stress responses. Early in the exposure, the predominant effect was on metabolic processes, while at later times, an immune-like response and cellular repair mechanisms dominated the expression pattern. Following removal of dichlorvos, the gene expression in the worms appeared to relatively rapidly return to steady-state levels.
  
  
  CONCLUSIONS
  The changes in gene expression observed in the worms following exposure to dichlorvos point towards two potential mechanisms of toxicity: inhibition of AChE and mitochondrial disruption.
authors: US Army Center for Environmental Health Research, Fort Detrick, MD, USA. john.a.lewis1@us.army.mil
authors: John A
authors: JA
authors: Lewis
authors: Elizabeth A
authors: EA
authors: Gehman
authors: Christine E
authors: CE
authors: Baer
authors: David A
authors: DA
authors: Jackson
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004006:Dichlorvos / Q000633:toxicity*; D051858:Forkhead Transcription Factors; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D009068:Movement / Q000187:drug effects; D009132:Muscles / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects; D010575:Pesticides / Q000633:toxicity*; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D010575:Pesticides; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D004006:Dichlorvos
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