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冠状动脉粥样硬化患者培养的成纤维细胞中放射敏感性增加及抗辐射DNA合成

Increased radiosensitivity and radioresistant DNA synthesis in cultured fibroblasts from patients with coronary atherosclerosis.

作者信息

Hannan M A, Khougeer F, Halees Z, Sanei A M, Khan B A

机构信息

Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

出版信息

Arterioscler Thromb. 1994 Nov;14(11):1761-6. doi: 10.1161/01.atv.14.11.1761.

DOI:10.1161/01.atv.14.11.1761
PMID:7947601
Abstract

Cultured skin fibroblasts from five patients with atherosclerosis who underwent coronary artery bypass graft surgery were compared with those from one ataxia telangiectasia (AT) homozygote, three AT heterozygotes, and five healthy subjects to determine their sensitivity to gamma radiation as determined by a colony survival assay. Fibroblasts from four of these patients were also compared with those from two AT homozygotes, two AT heterozygotes, and three healthy subjects to determine postirradiation [3H]thymidine incorporation, indicating the levels of radioresistant DNA synthesis (RDS). On the basis of colony survival assay, after long-term irradiation (at low dose rate, ie, 0.007 Gy/min), fibroblasts from all five patients with atherosclerosis exhibited radiosensitivity that was intermediate between that of the healthy subjects and that of patients with the known radiosensitive syndrome AT. However, there was a considerable interstrain difference in the radiosensitivity of fibroblasts from patients with atherosclerosis, with their mean D10 values (radiation dose resulting in 10% cell survival) varying between 2.3 and 6.2 Gy, whereas the mean D10 values for the cells from the AT homozygote, AT heterozygotes, and healthy subjects were 2.0, 3.8, and 9.0 Gy, respectively. One of the patients with atherosclerosis showed cellular radiosensitivity quite similar to that of the AT homozygote, up to 2% to 10% of survival levels after short- (at a dose rate of 8 Gy/min) and long-term irradiation, respectively. The results of [3H]thymidine incorporation showed an AT heterozygote-like RDS in fibroblasts from patients with atherosclerosis that appeared to be intermediate between that of AT homozygotes and that of healthy subjects, suggesting a partial deregulation of cell cycle in the patients with atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

对5例接受冠状动脉搭桥手术的动脉粥样硬化患者的培养皮肤成纤维细胞,与1例共济失调毛细血管扩张症(AT)纯合子、3例AT杂合子及5例健康受试者的细胞进行比较,通过集落存活试验确定其对γ射线的敏感性。还将其中4例患者的成纤维细胞与2例AT纯合子、2例AT杂合子及3例健康受试者的细胞进行比较,以确定辐照后[3H]胸腺嘧啶核苷掺入情况,这表明了抗辐射DNA合成(RDS)水平。基于集落存活试验,在长期辐照(低剂量率,即0.007 Gy/分钟)后,所有5例动脉粥样硬化患者的成纤维细胞表现出的辐射敏感性介于健康受试者与已知辐射敏感综合征AT患者之间。然而,动脉粥样硬化患者成纤维细胞的辐射敏感性存在相当大的株间差异,其平均D10值(导致10%细胞存活的辐射剂量)在2.3至6.2 Gy之间变化,而AT纯合子、AT杂合子及健康受试者细胞的平均D10值分别为2.0、3.8和9.0 Gy。其中1例动脉粥样硬化患者的细胞辐射敏感性与AT纯合子非常相似,在短时间(剂量率为8 Gy/分钟)和长期辐照后,存活水平分别高达2%至10%。[3H]胸腺嘧啶核苷掺入结果显示,动脉粥样硬化患者成纤维细胞中的RDS类似AT杂合子,似乎介于AT纯合子与健康受试者之间,提示动脉粥样硬化患者细胞周期存在部分失调。(摘要截短于250字)

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