Alteration of mitogen-activated protein kinase pathway after soman poisoning.
The p38 mitogen-activated protein kinase (MAPK) and activated MAPK transcription factors c-jun, c-myc, and elk-1 were investigated in rat enterocytes after sublethal poisoning with soman to study the pathogenetic mechanism of nonspecific long-term effects of nerve agents. Wistar rats were poisoned by intramuscular administration of soman at a dose 60 microg x kg(-1) (70% LD(50)) and sacrificed by cervical dislocation 3 and 5 days after poisoning. Control groups were administered physiologic saline instead of soman. Protein expression in immunohistochemically stained samples from colon transversum of control and poisoned rats was measured using image analysis. In comparison with control groups, activated p38 MAPK from soman-poisoned rats was significantly depressed at both time intervals. c-myc and c-jun expression was significantly increased 3 days after soman poisoning. On the other hand, a decrease in c-myc and c-jun expression was observed 5 days after soman poisoning. No changes in elk-1 expression were found. Long-term depression of MAPK pathway members might allow cells to proliferate in poisoned rats. This mechanism can be linked with apoptosis and carcinogenesis.
Osterreicher
Jan
J
Department of Radiation Biology, Faculty of Military Health Sciences, University of Defense, Hradec Kralove, Czech Republic.
Pejchal
Jaroslav
J
Kassa
Jiri
J
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D020895:Enterocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007273:Injections, Intramuscular; D007928:Lethal Dose 50; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D050807:ets-Domain Protein Elk-1; D012999:Soman; D048051:p38 Mitogen-Activated Protein Kinases