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自然本底辐射在维持 CGL1 人杂交模型系统基因组稳定性中的作用。

The Role of Natural Background Radiation in Maintaining Genomic Stability in the CGL1 Human Hybrid Model System.

机构信息

School of Natural Sciences, Laurentian University, Sudbury, Ontario, Canada.

Department of Radiation Oncology, Radiation and Cancer Biology Laboratories, and Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.

出版信息

Radiat Res. 2024 Oct 1;202(4):617-625. doi: 10.1667/RADE-23-00243.1.

DOI:10.1667/RADE-23-00243.1
PMID:39134062
Abstract

Natural background ionizing radiation is present on the earth's surface; however, the biological role of this chronic low-dose-rate exposure remains unknown. The Researching the Effects of the Presence and Absence of Ionizing Radiation (REPAIR) project is examining the impacts of sub-natural background radiation exposure through experiments conducted 2 km underground in SNOLAB. The rock overburden combined with experiment-specific shielding provides a background radiation dose rate 30 times lower than on the surface. We hypothesize that natural background radiation is essential for life and maintains genomic stability and that prolonged exposure to sub-background environments will be detrimental to biological systems. To evaluate this, human hybrid CGL1 cells were continuously cultured in SNOLAB and our surface control laboratory for 16 weeks. Cells were assayed every 4 weeks for growth rate, alkaline phosphatase (ALP) activity (a marker of cellular transformation in the CGL1 system), and the expression of genes related to DNA damage and cell cycle regulation. A subset of cells was also exposed to a challenge radiation dose (0.1 to 8 Gy of X rays) and assayed for clonogenic survival and DNA double-strand break induction to examine if prolonged sub-background exposure alters the cellular response to high-dose irradiation. At each 4-week time point, sub-background radiation exposure did not significantly alter cell growth rates, survival, DNA damage, or gene expression. However, cells cultured in SNOLAB showed significantly higher ALP activity, a marker of carcinogenesis in these cells, which increased with longer exposure to the sub-background environment, indicative of neoplastic progression. Overall, these data suggest that sub-background radiation exposure does not impact growth, survival, or DNA damage in CGL1 cells but may lead to increased rates of neoplastic transformation, highlighting a potentially important role for natural background radiation in maintaining normal cellular function and genomic stability.

摘要

天然本底电离辐射存在于地球表面;然而,这种慢性低剂量率暴露的生物学作用尚不清楚。研究存在和不存在电离辐射的影响(REPAIR)项目正在通过在 SNOLAB 地下 2 公里处进行的实验来检查亚天然本底辐射暴露的影响。岩石覆盖层加上实验专用屏蔽层提供了比地表低 30 倍的背景辐射剂量率。我们假设天然本底辐射对生命是必不可少的,它维持着基因组的稳定性,而长时间暴露于亚背景环境将对生物系统有害。为了评估这一点,人类杂交 CGL1 细胞在 SNOLAB 和我们的地表对照实验室中连续培养了 16 周。每隔 4 周对细胞进行一次生长速率、碱性磷酸酶(ALP)活性(CGL1 系统中细胞转化的标志物)以及与 DNA 损伤和细胞周期调控相关基因表达的测定。还对一部分细胞进行了挑战辐射剂量(0.1 至 8Gy 的 X 射线)暴露,并对集落形成存活和 DNA 双链断裂诱导进行了测定,以检查长时间的亚背景暴露是否改变了细胞对高剂量照射的反应。在每个 4 周的时间点,亚背景辐射暴露并未显著改变细胞生长速率、存活率、DNA 损伤或基因表达。然而,在 SNOLAB 中培养的细胞显示出明显更高的 ALP 活性,这是这些细胞癌变的标志物,随着对亚背景环境的暴露时间延长,ALP 活性增加,表明肿瘤进展。总体而言,这些数据表明,亚背景辐射暴露不会影响 CGL1 细胞的生长、存活或 DNA 损伤,但可能导致肿瘤转化率增加,突出了天然本底辐射在维持正常细胞功能和基因组稳定性方面的潜在重要作用。

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