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Soman and VX: different effect on cellular signalling

Jaroslav Pejchal, Jan Österreicher, Jiří Kassa, Aleš Tichý, Zuzana Šinkorová, Lenka Zárybnická, Klára Kubelková, Kamil Kuča

. 2012 ; 10 (1) : 51-61.

Jazyk angličtina Země Česko

Perzistentní odkaz   https://www.medvik.cz/link/bmc12007112

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.

Citace poskytuje Crossref.org

Obsahuje tabulky

Bibliografie atd.

Literatura

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$a 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.
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