SUMMARY
The purpose of our study was to examine the early expression of p21 and activated transcription factors ATF-2, CREB, Elk-1, p53 after soman and VX
poisoning, to throw light on the pathogenetic mechanism of nerve agent-induced non-specific effects. Male Wistar rats were i.m. poisoned by soman
(60 microg.kg-1 - 70% LD50) or VX (8 microg.kg-1 - 70% LD50). Samples were taken 4, 24, and 72 hours
after poisoning, immunohistochemically stained and phospho-ATF-2Thr-69/71, phospho-CREBSer-133,
phospho-Elk-1Ser-383, phospho-p53Ser-15, and protein p21 expressions were measured using computer Image analysis in apical and
cryptal enterocytes of the colon transversum. After soman poisoning, we observed an increased phospho-CREB in cryptal enterocytes 4, 24, and 72 h
after poisoning, while apical enterocytes expressed increased phospho-CREB only 72 h after intoxication. Phospho-Elk-1 significantly dropped 4 and
24 h after soman poisoning in the cryptal compartment. Activation of ATF-2 and p53 and expression of p21 were not changed 4, 24, and 72 h after
soman poisoning. VX poisoning did not change any of measured parameters. Soman and VX showed a different effect on cellular signalling. Soman seems
to cause additional effects, which are not related to the basic mechanism of nerve agent-induced toxicity and which temporarily suppress promitotic
pathways of proliferating cells and persist in cells during the differentiation process.
KEY WORDS
soman; VX; ATF-2; CREB, Elk-1; p21; p53; enterocyte; image analysis
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