TY - JOUR
T1 - Influence of paraoxon (POX) and parathion (PAT) on apoptosis
T2 - A possible mechanism for toxicity in low-dose exposure
AU - Saleh, A. M.
AU - Vjayasarathy, C.
AU - Fernandez-Cabezudo, M.
AU - Taleb, M.
AU - Petroianu, G.
PY - 2003/1
Y1 - 2003/1
N2 - 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 IC50 POX is a potent inducer of apoptosis, as opposed to PAT that shows little apoptotic effect.
AB - 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 IC50 POX is a potent inducer of apoptosis, as opposed to PAT that shows little apoptotic effect.
KW - Apoptosis
KW - Caspase
KW - Organophosphate
KW - Paraoxon
KW - Parathion
UR - http://www.scopus.com/inward/record.url?scp=0037255488&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037255488&partnerID=8YFLogxK
U2 - 10.1002/jat.880
DO - 10.1002/jat.880
M3 - Review article
C2 - 12518333
AN - SCOPUS:0037255488
SN - 0260-437X
VL - 23
SP - 23
EP - 29
JO - Journal of Applied Toxicology
JF - Journal of Applied Toxicology
IS - 1
ER -