Influence of paraoxon (POX) and parathion (PAT) on apoptosis: a possible mechanism for toxicity in low-dose exposure.
The acute effects of poisoning with organophosphorus compounds (OPCs) are well known and have been described extensively. Most of the clinical symptoms are due to inhibition of acetylcholinesterase. Although acute OPC poisoning is a well-established clinical entity, the existence of chronic poisoning due to exposure to low levels of OPC (below the threshold required for cholinergic clinical symptoms) is a hotly debated issue. Recent studies have suggested the involvement of OPCs in apoptotic processes. However, the mechanisms by which they modulate this process are poorly investigated. In the present study we evaluated the toxic effect of different concentrations of paraoxon (POX) and parathion (PAT) in murine EL4 T lymphocytes. We examined cellular responses, including induction of apoptosis, involvement of a caspase cascade, the activity of effector caspase (caspase-3) and the biochemical and morphological changes that are the hallmarks of classical apoptosis. The results of our study indicate that at doses below IC(50) POX is a potent inducer of apoptosis, as opposed to PAT that shows little apoptotic effect.
Saleh
A M
AM
United Arab Emirates University, Faculty of Medicine & Health Sciences, Department of Biochemistry, Al Ain, United Arab Emirates. asaleh@uaeu.ac.ae
Vijayasarathy
C
C
Fernandez-Cabezudo
M
M
Taleb
M
M
Petroianu
G
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D020128:Inhibitory Concentration 50; D007306:Insecticides / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D010261:Paraoxon / Q000633:toxicity*; D010278:Parathion / Q000633:toxicity*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism
D007306:Insecticides; D011994:Recombinant Proteins; D010278:Parathion; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D010261:Paraoxon