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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Radiation-induced non-targeted response in vivo: role of the TGFýý-TGFBR1-COX-2 signalling pathway.

Authors: Chai, Y; Lam, R K K; Calaf, G M; Zhou, H; Amundson, S; Hei, T K

Published In Br J Cancer, (2013 Mar 19)

Abstract: Previous studies from our group and others have shown that cyclooxygenase-2 (COX-2) has an essential role in radiation-induced non-targeted responses and genomic instability in vivo. However, the signalling pathways involved in such effects remain unclear.A 1ýýýcm(2) area (1ýýýcm ýý 1ýýýcm) in the lower abdominal region of gpt delta transgenic mice was irradiated with 5ýýýGy of 300ýýýkeV X-rays. Nimesulide, a selective COX-2 inhibitor, was given to mice for five consecutive days before irradiation. Changes in transforming growth factor-beta (TGF-ýý) and TGF-ýý receptor type-1 (TGFBR1) mediated signalling pathways, in the out of radiation field lung and liver tissues were examined.While the plasma level of cytokines remained unchanged, the expression of TGF-ýý and its receptors was elevated in non-targeted lung tissues after partial body irradiation. In contrast to the predominant expression of TGF-ýý in stromal and alveolar cells, but not in bronchial epithelial cells, TGF-ýý receptors, especially TGFBR1 were significantly elevated in non-targeted bronchial epithelial cells, which is consistent with the induction of COX-2. The different expression levels of TGFBR1 between liver and lung resulted in a tissue specific induction of COX-2 in these two non-targeted tissues. Multiple TGF-ýý induced signalling pathways were activated in the non-targeted lung tissues.The TGFýý-TGFBR1-COX-2 Signalling Pathway has a critical role in radiation-induced non-targeted response in vivo.

PubMed ID: 23412109 Exiting the NIEHS site

MeSH Terms: Animals; Bystander Effect/radiation effects; Cyclooxygenase 2 Inhibitors/pharmacology; Cyclooxygenase 2/metabolism*; Liver/metabolism; Liver/radiation effects*; Lung/metabolism; Lung/radiation effects*; Mice; Mice, Transgenic; Organ Specificity; Protein-Serine-Threonine Kinases/metabolism*; Receptors, Transforming Growth Factor beta/metabolism*; Signal Transduction/radiation effects*; Sulfonamides/pharmacology; Transforming Growth Factor beta/metabolism*; X-Rays

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