In vitro X-ray sensitivity in ataxia telangiectasis homozygote and heterozygote skin fibroblasts under oxic and hypoxic conditions.
In vitro X-ray sensitivity in ataxia telangiectasis homozygote and heterozygote skin fibroblasts under oxic and hypoxic conditions.
复制标题
共济失调毛细血管扩张纯合子和杂合子皮肤成纤维细胞在有氧和缺氧条件下的体外 X 射线敏感性。
作者：
T. Kinsella;J. Mitchell;S. McPherson;A. Russo;F. Tietze
摘要共济失调毛细血管扩张症（AT）的合子患癌症的风险增加，特别是在45岁以前。体外培养的某些AT hA©tA©合子的皮肤成纤维细胞对X射线照射的致死效应的敏感性高于AT纯合子和正常对照成纤维细胞，这种体外集落形成试验已被建议作为临床筛选假定的AT hA©tA©合子（AT hA©tA©合子的亲属）以鉴定癌症高危个体。我们研究了来自三个AT家族和两个正常对照的培养皮肤成纤维细胞对X射线照射的反应，以进一步探讨这些观察结果。与以前的报道相反，我们没有发现这些家族中来自专性AT hA©tA©合子的成纤维细胞与正常对照成纤维细胞相比在辐射存活率（D 0）方面有任何差异。我们报告了正常氧增强比，比较了缺氧与空气条件下培养的AAE卵合子、hA©tA©卵合子和正常对照的成纤维细胞的放射敏感性（D 0）。此外，我们报告AT hA©tA©合子和正常对照成纤维细胞的对数期细胞的谷胱甘肽含量没有差异，我们得出结论，AT hA©tA©合子皮肤成纤维细胞在空气和缺氧中的辐射存活与正常对照细胞系相似。低的平板接种效率、空气和缺氧中的可变外推数以及某些细胞系中的细胞密度效应使得难以确定这些细胞的有意义的氧增强比率。我们没有发现缺氧条件下对X射线照射的反应是AT hA©tA©合子的有用体外标记。引言AT 2是一种常染色体隐性遗传的人类疾病，其发病率约为1/40，000活产婴儿（16）。这种遗传性疾病在纯合子中有许多有趣的表型表现，包括：中枢神经系统、皮肤和血管内的进行性变性（或细胞丢失）; T淋巴细胞和B淋巴细胞功能的免疫缺陷;癌症、原发性淋巴瘤和白血病的风险增加;治疗性照射后正常组织损伤增强（8，16）。体外培养的AT纯合子皮肤成纤维细胞和淋巴细胞对X射线杀伤的敏感性增加
ABSTRACTHA©tA©rozygotesfor ataxia telangiectasia (AT) are reported tohave an increased risk of cancer especially prior to age 45years. Cultured skin fibroblasts from some AT hA©tA©rozygotesare reported to show increased sensitivity to the lethal effectsof X-irradiation under hypoxia which is intermediate betweenthe response of AT homozygote and normal control fibroblasts.This in vitro colony formation assay has been suggested as aclinical screen for presumed AT hA©tA©rozygotes(relatives of AThomozygotes) to identify individuals at high risk for cancer. Ithas also been speculated that this radiosensitivity under hypoxia may represent a previously unrecognized DNA repairdefect.We have studied the response to X-irradiation of culturedskin fibroblasts from three AT families and two normal controlsto further explore these observations. In contrast to the previous report, we did not find any difference in radiation survival(D0) of fibroblasts from obligate AT hA©tA©rozygotesin thesefamilies compared to normal control fibroblasts. We reportnormal oxygen enhancement ratios comparing radiosensitivity(D0) under hypoxia to air for the fibroblast cultures of AThomozygotes, hA©tA©rozygotes,and normal controls. Additionally, we report no difference in glutathione content of log-phasecells in AT hA©tA©rozygotesand normal control fibroblasts.We conclude that the radiation survival in air and hypoxia ofAT hA©tA©rozygoteskin fibroblasts is similar to that of normalcontrol cell lines. Low plating efficiency, variable extrapolationnumbers in air and hypoxia, and cell density effects in somecell lines make it difficult to determine a meaningful oxygenenhancement ratio for these cells. We do not find the responseto X-irradiation under hypoxia to be a useful in vitro marker forAT hA©tA©rozygotes.INTRODUCTIONAT2 is an autosomal recessive human disease with a reportedfrequency of approximately 1 of 40,000 live births (16). Thisgenetic disease has a number of interesting phenotypic manifestations in the homozygote including: a progressive degeneration (or cell loss) within the central nervous system, skin,and blood vessels; an immunological defect of both T- and B-lymphocyte function; an increased risk of cancer, primarilylymphoma and leukemia; and enhanced normal tissue damagefollowing therapeutic irradiation (8, 16). In vitro work on cultured skin fibroblasts and lymphocytes from AT homozygoteshas demonstrated an increased sensitivity to killing by X-rays
碘 125 对共济失调毛细血管扩张成纤维细胞的放射毒性。
DOI：
10.1016/0005-2787(81)90218-5
发表时间：
1981
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Ritter,MA
通讯作者：
Ritter,MA