PMID- 15850933 OWN - NLM STAT- MEDLINE DCOM- 20050607 LR - 20220316 IS - 0360-3016 (Print) IS - 0360-3016 (Linking) VI - 62 IP - 1 DP - 2005 May 1 TI - Mechanism and modification of gastrointestinal soft tissue response to radiation: role of growth factors. PG - 273-8 AB - PURPOSE: The negative effects of radiation on the bowel critically limit the treatment doses possible for tumors in the abdomen. The purpose of the present study was to measure mRNA levels of inflammatory cytokines in abdominally irradiated mouse bowel. METHODS AND MATERIALS: Eight- to 12-week-old DBA mice were irradiated to the whole bowel in single fractions of 0 (mock irradiation), 12.5, or 13.5 Gy, and sacrificed 18-25 weeks thereafter. Gross bowel reactions were scored for bowel retraction, bowel wall thickening, mesenteric telangiectasia, and petechia. Tissues were snap frozen and processed for RNase protection assay or reverse transcription polymerase chain reaction assay, or both. Transforming growth factor beta1 (TGFbeta1), TGFbeta2, TGFbeta3, tumor necrosis factor alpha, interleukin-6, and interferon gamma mRNA were measured. RESULTS: Radiation at 12.5 Gy and at 13.5 Gy produced significant bowel damage. Levels of all cytokines in irradiated mice were significantly increased (p < 0.05). CONCLUSIONS: Late radiation-related bowel fibrovascular toxicity includes cytokine signal pathways that parallel those of many other normal tissues. These cytokine responses include elevations of tumor necrosis factor alpha, TGFbeta1, and interleukin-6. There exist approaches for lowering these cytokine levels that do not also protect tumor, and thus a therapeutic gain is expected. Opportunities to use these cytokine measurements both to predict clinical toxicity and to develop interventions are discussed. FAU - Okunieff, Paul AU - Okunieff P AD - Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY 14642, USA. Paul.Okunieff@URMC.Rochester.edu FAU - Cornelison, Terri AU - Cornelison T FAU - Mester, Marcelo AU - Mester M FAU - Liu, Weimin AU - Liu W FAU - Ding, Ivan AU - Ding I FAU - Chen, Yuchyau AU - Chen Y FAU - Zhang, Hong AU - Zhang H FAU - Williams, Jacqueline P AU - Williams JP FAU - Finkelstein, Jacob AU - Finkelstein J LA - eng GR - 1R13CA100307-01/CA/NCI NIH HHS/United States GR - P01-CA11051-30/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 RN - 0 (Cytokines) RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 0 (Tgfb1 protein, mouse) RN - 0 (Tgfb3 protein, mouse) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) RN - 0 (Transforming Growth Factor beta2) RN - 0 (Transforming Growth Factor beta3) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Cytokines/*metabolism MH - Interferon-gamma/metabolism MH - Interleukin-6/metabolism MH - Intestinal Mucosa/metabolism MH - Intestines/*radiation effects MH - Mice MH - Mice, Inbred DBA MH - RNA, Messenger/metabolism MH - Radiation Injuries, Experimental/*metabolism MH - Transforming Growth Factor beta/metabolism MH - Transforming Growth Factor beta1 MH - Transforming Growth Factor beta2 MH - Transforming Growth Factor beta3 MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2005/04/27 09:00 MHDA- 2005/06/09 09:00 CRDT- 2005/04/27 09:00 PHST- 2005/01/25 00:00 [received] PHST- 2005/01/25 00:00 [revised] PHST- 2005/01/25 00:00 [accepted] PHST- 2005/04/27 09:00 [pubmed] PHST- 2005/06/09 09:00 [medline] PHST- 2005/04/27 09:00 [entrez] AID - S0360-3016(05)00227-0 [pii] AID - 10.1016/j.ijrobp.2005.01.034 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 2005 May 1;62(1):273-8. doi: 10.1016/j.ijrobp.2005.01.034.