CAJ | 학술논문

高能α粒子辐射所致基因组DNA损伤形式为复杂的簇集损伤,修复难度大,生物效应严重,目前尚缺乏有效防护药物.前期发现香兰素衍生物VND3207具有抗氧化损伤、促进DNA双链断裂损伤修复的作用,能有效防护低传能线密度(LET)γ射线诱发细胞凋亡和基因组损伤.本研究旨在探讨VND3207对高能α粒子辐射诱发人成纤维细胞基因组DNA损伤的防护效应.细胞克隆形成实验表明,VND3207无论是照射前加药还是照射后加药作用均能增强人成纤维HFS细胞对α粒子的辐射损伤抗性.通过中性单细胞凝胶电泳(彗星电泳)、γ-H2AX免疫荧光簇集点、γ-H2AX蛋白表达水平、细胞微核等多个基因组DNA损伤指标分析,表明了VND3207对α粒子辐射诱发细胞基因组DNA损伤的有效防护作用,其在5～10μmol/L浓度下,就可产生显著辐射防护效果,既能减轻α粒子辐射诱发细胞DNA的原初损伤水平,又能提高细胞的DNA修复能力.因此,VND3207具有维护高能粒子辐照细胞的基因组稳定性的作用,有开发成为抗高LET辐射损伤新药的价值.
고능α입자복사소치기인조DNA손상형식위복잡적족집손상,수복난도대,생물효응엄중,목전상결핍유효방호약물.전기발현향란소연생물VND3207구유항양화손상、촉진DNA쌍련단렬손상수복적작용,능유효방호저전능선밀도(LET)γ사선유발세포조망화기인조손상.본연구지재탐토VND3207대고능α입자복사유발인성섬유세포기인조DNA손상적방호효응.세포극륭형성실험표명,VND3207무론시조사전가약환시조사후가약작용균능증강인성섬유HFS세포대α입자적복사손상항성.통과중성단세포응효전영(혜성전영)、γ-H2AX면역형광족집점、γ-H2AX단백표체수평、세포미핵등다개기인조DNA손상지표분석,표명료VND3207대α입자복사유발세포기인조DNA손상적유효방호작용,기재5～10μmol/L농도하,취가산생현저복사방호효과,기능감경α입자복사유발세포DNA적원초손상수평,우능제고세포적DNA수복능력.인차,VND3207구유유호고능입자복조세포적기인조은정성적작용,유개발성위항고LET복사손상신약적개치.
As a high linear energy transfer(LET)radiation,α particles mainly induce DNA clustered damage with low repair efficiency and serious biological effects.There is still no effective radioprotection agent available against the biological detriments induced by α particles.The vanillin derivative VND3207 is a novel radioprotection agent with an antioxidant potentiality and protective effects against the genomic DNA damage and apoptosis induced by low LET γ-ray.The present study is designed to determine the radiopmtective effect of VND3207 against the genomic DNA damage of human fibroblast HFS cells induced by high LET α particles.The clonogenic survival assay shows that VND3207 can significantly enhance radioresistance of HFS cells to the irradiation of α particles,no matter the cells are treated with VND3207 before or after irradiation.Multiple indicators of DNA damage detection,including single cell gel electrophoresis,immnuo-fluorescent γ-H2AX foci,γ-H2AX protein expression and micronuclei assay,demonstrate that VND3207 Call effectively decrease the initial DNA double-strand break level as well as increase the cellular DNA repair capacity and redHee the residual damage level.The effective concentration is as low as 10～20 mol/L.In conclusion,VND3207 has radioprotective effects on cell survival and genomic stability against the irradiation of α particles,and it is of value to develop radioprotective drugs against high LET radiation.