Transcriptional response of ex vivo human skin to ionizing radiation: comparison between low- and high-dose effects.

Transcriptional response of ex vivo human skin to ionizing radiation: comparison between low- and high-dose effects.
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DOI:
10.1667/rr2524.1
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发表时间:
2012-01
期刊:
影响因子:
3.4
通讯作者:
Rocke DM
Rocke DM
中科院分区:
医学3区
文献类型:
--
作者:
Albrecht H;Durbin-Johnson B;Yunis R;Kalanetra KM;Wu S;Chen R;Stevenson TR;Rocke DM

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虽然人类暴露于低剂量电离辐射可通过各种来源发生,包括自然、医疗、职业和意外,但人类对低剂量电离辐射的真正风险仍知之甚少。本文分析和比较了体外培养的人皮肤在低剂量(0.05Gy射线)和高剂量(5Gy射线)照射后的整体转录反应,以及照射后0、2、8和30h的培养时间(0Gy0)。对低剂量和高剂量的反应在数量和质量上都不同。差异表达基因分为三组:(1)独特的基因,定义为对0.05或5Gy两种射线都有反应,但不同时对培养时间有反应;(2)特定基因,定义为对0.05或5Gy两种射线都有反应,但不同时对培养时间有反应;(3)非剂量依赖性反应基因。在体外照射的皮肤中观察到对低剂量和高剂量转录反应的主要差异是双重的。首先,0.05Gy射线对基因表达的调节是暂时的,而对5Gy射线的响应,观察到有限数量的基因持续表达修饰基因。其次,在急性低剂量暴露后,tP53和转化生长因子β靶基因都没有被调节,这表明依赖tP53的dna损伤反应要么没有被触发,要么只是短暂地被触发。
Although human exposure to low-dose ionizing radiation can occur through a variety of sources, including natural, medical, occupational and accidental, the true risks of low-dose ionizing radiation are still poorly understood in humans. Here, the global transcriptional responses of human skin after ex vivo exposure to low (0.05 Gy) and high (5 Gy) doses of X rays and of time in culture (0 Gy) at 0, 2, 8 and 30 h postirradiation were analyzed and compared. Responses to low and high doses differed quantitatively and qualitatively. Differentially expressed genes fell into three groups: (1) unique genes defined as responsive to either 0.05 or 5 Gy but not both and also responsive to time in culture, (2) specific genes defined as responsive to either 0.05 or 5 Gy but not both and not responsive to time in culture, and (3) dose-independent responsive genes. Major differences observed in ex vivo irradiated skin between transcriptional responses to low or high doses were twofold. First, gene expression modulated by 0.05 Gy was transient, while in response to 5 Gy persistence of modified gene expression was observed for a limited number of genes. Second, neither TP53 nor TGFβ target genes were modulated after exposure to an acute low dose, suggesting that the TP53-dependent DNA damage response either was not triggered or was triggered only briefly.
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