J Appl Biomed 10:51-61, 2012 | DOI: 10.2478/v10136-011-0018-z

Soman and VX: different effect on cellular signalling

Jaroslav Pejchal1, Jan Österreicher2, Jiří Kassa3, Aleš Tichý2, Zuzana Šinkorová2, Lenka Zárybnická2, Klára Kubelková1, Kamil Kuča1,4,*
1 Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
2 Department of Radiation Biology, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
3 Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
4 Center for Biomedical Research, University Hospital Hradec Králové, Hradec Králové, Czech Republic

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 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 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.

Keywords: soman; VX; ATF-2; CREB; Elk-1; p21; p53; enterocyte; image analysis

Received: May 16, 2011; Revised: July 26, 2011; Published: March 31, 2012  Show citation

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Pejchal J, Österreicher J, Kassa J, Tichý A, Šinkorová Z, Zárybnická L, et al.. Soman and VX: different effect on cellular signalling. J Appl Biomed. 2012;10(1):51-61. doi: 10.2478/v10136-011-0018-z.
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