title: Effects of paraoxon on neuronal and lymphocytic cholinergic systems.
abstract: The cholinergic system in lymphocytes is hypothesized to be a key target for neurotoxic organophosphates (OPs). The present study determined the comparative effects of paraoxon, the active metabolite of OP-parathion, which is detected in the human neuroblastoma line, SH-SY5Y, and leukemic T-lymphocytes, MOLT-3, in vitro. Paraoxon induced cytotoxic effects in a dose- and time-dependent manner in both cells. Further, the paraoxon-induced modulatory effects were comparable despite different cell types, including over-expression of N-terminus acetylcholinesterase (N-AChE) protein, a marker of apoptosis, down-regulations of mRNA encoding M1, M2, and M3 muscarinic acetylcholine receptors (mAChRs), and induction in expression of c-Fos gene, an indication of certain mAChR subtype(s) activation. Furthermore, the non-selective cholinergic antagonist atropine partially attenuated the paraoxon-induced N-AChE and c-Fos activations in both types of cells. These results provide initial and additional information that OPs may similarly induce neuro- and immuno-toxic effects through mAChRs activation, and they underline the potential of using lymphocytes for assessing OPs-induced neurotoxicity.
authors.affiliation: Inter-University Program in Environmental Toxicology, Technology, and Management, Asian Institute of Technology, Mahidol University, and Chulabhorn Research Institute, Bangkok 10210, Thailand.
authors.forename: Tanvisith
authors.initials: T
authors.lastname: Charoenying
authors.forename: Tawit
authors.initials: T
authors.lastname: Suriyo
authors.forename: Apinya
authors.initials: A
authors.lastname: Thiantanawat
authors.forename: Sansanee C
authors.initials: SC
authors.lastname: Chaiyaroj
authors.forename: Preeda
authors.initials: P
authors.lastname: Parkpian
authors.forename: Jutamaad
authors.initials: J
authors.lastname: Satayavivad
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004396:Coloring Agents; D016762:Genes, fos / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D008214:Lymphocytes / Q000187:drug effects*; D018721:Muscarinic Agonists / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D010261:Paraoxon / Q000633:toxicity*; D010275:Parasympathetic Nervous System / Q000166:cytology* / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D043643:Receptor, Muscarinic M1 / Q000187:drug effects; D043585:Receptor, Muscarinic M2 / Q000187:drug effects; D043587:Receptor, Muscarinic M3 / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D002800:Cholinesterase Inhibitors; D004396:Coloring Agents; D007202:Indicators and Reagents; D018721:Muscarinic Agonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D013778:Tetrazolium Salts; D013844:Thiazoles; D000110:Acetylcholinesterase; C022616:thiazolyl blue; D010261:Paraoxon