PMID- 18563361 OWN - NLM STAT- MEDLINE DCOM- 20080919 LR - 20131121 IS - 0253-6269 (Print) IS - 0253-6269 (Linking) VI - 31 IP - 6 DP - 2008 Jun TI - Effect of proton beam on blood vessel formation in early developing zebrafish (Danio rerio) embryos. PG - 779-85 LID - 10.1007/s12272-001-1226-1 [doi] AB - Proton beam therapy can kill tumor cells while saving normal cells because of its specific energy delivery properties and so is used to various tumor patients. However, the effect of proton beam on angiogenesis in the development of blood vessels has not been determined. Here we used the zebrafish model to determine in vivo whether proton beam inhibits angiogenesis. Flk-1-GFP transgenic embryos irradiated with protons (35 MeV, spread out Bragg peak, SOBP) demonstrated a marked inhibition of embryonic growth and an altered fluorescent blood vessel development in the trunk region. When cells were stained with acridine orange to evaluate DNA damage, the number of green fluorescent cell death spots was increased in trunk regions of irradiated embryos compared to non-irradiated control embryos. Proton beam also significantly increased the cell death rate in human umbilical vein endothelial cells (HUVEC), but pretreatment with N-acetyl cystein (NAC), an antioxidant, reduced the proton-induced cell death rate (p<0.01). Moreover, pretreatment with NAC abrogated the inhibition of trunk vessel development and prevented the trunk malformation caused by proton irradiation. In conclusion, proton irradiation significantly inhibited in vivo vascular development possibly due to increased vascular cell death via reactive oxygen species formation. FAU - Jang, Gun Hyuk AU - Jang GH AD - School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, 702-701, Korea. FAU - Ha, Ji-Hong AU - Ha JH FAU - Huh, Tae-Lin AU - Huh TL FAU - Lee, You Mie AU - Lee YM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080619 PL - Korea (South) TA - Arch Pharm Res JT - Archives of pharmacal research JID - 8000036 RN - 0 (Antioxidants) RN - 0 (Protons) RN - 0 (Reactive Oxygen Species) RN - 0 (Recombinant Fusion Proteins) RN - 0 (enhanced green fluorescent protein) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/pharmacology MH - Animals MH - Animals, Genetically Modified MH - Antioxidants/pharmacology MH - Blood Vessels/drug effects/embryology/metabolism/*radiation effects MH - Cell Death/radiation effects MH - Cells, Cultured MH - DNA Damage MH - Dose-Response Relationship, Radiation MH - Endothelial Cells/metabolism/pathology/radiation effects MH - Green Fluorescent Proteins/metabolism MH - Humans MH - Neovascularization, Physiologic/drug effects/*radiation effects MH - *Protons MH - Reactive Oxygen Species/metabolism MH - Recombinant Fusion Proteins/metabolism MH - Vascular Endothelial Growth Factor Receptor-2/genetics/metabolism MH - Zebrafish/*embryology/genetics/metabolism EDAT- 2008/06/20 09:00 MHDA- 2008/09/20 09:00 CRDT- 2008/06/20 09:00 PHST- 2008/04/01 00:00 [received] PHST- 2008/05/08 00:00 [accepted] PHST- 2008/04/13 00:00 [revised] PHST- 2008/06/20 09:00 [pubmed] PHST- 2008/09/20 09:00 [medline] PHST- 2008/06/20 09:00 [entrez] AID - 10.1007/s12272-001-1226-1 [doi] PST - ppublish SO - Arch Pharm Res. 2008 Jun;31(6):779-85. doi: 10.1007/s12272-001-1226-1. Epub 2008 Jun 19.