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PNAS:测量辐射的附带损伤

来源:EurekAlert!中文版 2008-08-19 15:11

科学家发现了邻近受辐射细胞的细胞也被损伤的证据,这一发现可能促使人们对人工或自然辐射的安全剂量重新评估。

Anna Saran及其同事通过研究电离辐射对小鼠的脑的效应,从而开发了一种能测量动物的辐射损伤的技术。这组作者发现在小鼠小脑距离接触辐射的地方不远的细胞遭受了DNA损伤并产生了细胞凋亡(即程序性细胞死亡),即便那片特定区域被铅屏蔽。实验小鼠的一个对辐射敏感的基因(称为patched基因)有一个突变,这让它们更容易患癌症。这些小鼠遭受了辐射的长期效应,而对照组的小鼠只遭受了短期损伤。此前在细胞培养中观察到了这种附带损伤,而且被认为是由于直接接触或者被辐射损伤的细胞之间的化学通讯造成的。

这组科学家说,这种新技术将提供一种测量整个生物体的辐射损伤的方法。(生物谷Bioon.com)

生物谷推荐原始出处:

PNAS published August 18, 2008, doi:10.1073/pnas.0804186105

Oncogenic bystander radiation effects in Patched heterozygous mouse cerebellum

Mariateresa Mancuso*, Emanuela Pasquali?, Simona Leonardi*, Mirella Tanori*, Simonetta Rebessi*, Vincenzo Di Majo*, Simonetta Pazzaglia*, Maria Pia Toni?, Maria Pimpinella?, Vincenzo Covelli*, and Anna Saran*,§

Abstract

The central dogma of radiation biology, that biological effects of ionizing radiation are a direct consequence of DNA damage occurring in irradiated cells, has been challenged by observations that genetic/epigenetic changes occur in unexposed “bystander cells” neighboring directly-hit cells, due to cell-to-cell communication or soluble factors released by irradiated cells. To date, the vast majority of these effects are described in cell-culture systems, while in vivo validation and assessment of biological consequences within an organism remain uncertain. Here, we describe the neonatal mouse cerebellum as an accurate in vivo model to detect, quantify, and mechanistically dissect radiation-bystander responses. DNA double-strand breaks and apoptotic cell death were induced in bystander cerebellum in vivo. Accompanying these genetic events, we report bystander-related tumor induction in cerebellum of radiosensitive Patched-1 (Ptch1) heterozygous mice after x-ray exposure of the remainder of the body. We further show that genetic damage is a critical component of in vivo oncogenic bystander responses, and provide evidence supporting the role of gap-junctional intercellular communication (GJIC) in transmission of bystander signals in the central nervous system (CNS). These results represent the first proof-of-principle that bystander effects are factual in vivo events with carcinogenic potential, and implicate the need for re-evaluation of approaches currently used to estimate radiation-associated health risks.

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