Soman and VX: different effect on cellular signalling

The purpose of our study was to examine the early expression of p21 and activated transcription factorsATF-2, CREB, Elk-1, p53 after soman and VX poisoning, to throw light on the pathogenetic mechanism ofnerve agent-induced non-specific effects. Male Wistar rats were i.m. poisoned by soman (60 μg.kg-1 – 70%LD50) or VX (8 μg.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 andcryptal enterocytes of the colon transversum. After soman poisoning, we observed an increasedphospho-CREB in cryptal enterocytes 4, 24, and 72 h after poisoning, while apical enterocytes expressedincreased phospho-CREB only 72 h after intoxication. Phospho-Elk-1 significantly dropped 4 and 24 h aftersoman poisoning in the cryptal compartment. Activation of ATF-2 and p53 and expression of p21 were notchanged 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 suppresspromitotic pathways of proliferating cells and persist in cells during the differentiation process.