Jake Pirkkanen, Taylor Laframboise, Jayden Peterson, Alyssa Labelle, Forest Mahoney, Michel Lapointe, Marc S Mendonca, T C Tai, Simon J Lees, Sujeenthar Tharmalingam, Douglas R Boreham, Christopher Thome
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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.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Role of Natural Background Radiation in Maintaining Genomic Stability in the CGL1 Human Hybrid Model System.\",\"authors\":\"Jake Pirkkanen, Taylor Laframboise, Jayden Peterson, Alyssa Labelle, Forest Mahoney, Michel Lapointe, Marc S Mendonca, T C Tai, Simon J Lees, Sujeenthar Tharmalingam, Douglas R Boreham, Christopher Thome\",\"doi\":\"10.1667/RADE-23-00243.1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Natural background ionizing radiation is present on the earth's surface; however, the biological role of this chronic low-dose-rate exposure remains unknown. 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引用次数: 0
摘要
地球表面存在天然本底电离辐射;然而,这种长期低剂量辐射的生物作用仍然未知。电离辐射存在和不存在的影响研究(REPAIR)项目正在通过在 SNOLAB 地下 2 千米处进行的实验,研究亚天然本底辐射照射的影响。岩石覆盖层与特定实验屏蔽相结合,提供了比地面低 30 倍的本底辐射剂量率。我们假设,天然本底辐射是生命所必需的,并能维持基因组的稳定性,而长期暴露在亚本底辐射环境中将会对生物系统造成损害。为了评估这一点,我们在 SNOLAB 和我们的表面控制实验室连续培养人类杂交 CGL1 细胞 16 周。每 4 周对细胞的生长率、碱性磷酸酶 (ALP) 活性(CGL1 系统中细胞转化的标志)以及 DNA 损伤和细胞周期调节相关基因的表达进行一次检测。还有一部分细胞暴露于挑战辐射剂量(0.1 至 8 Gy 的 X 射线),并进行克隆存活率和 DNA 双链断裂诱导测定,以研究长期的亚背景暴露是否会改变细胞对高剂量辐照的反应。在每个 4 周的时间点,亚背景辐照都不会显著改变细胞的生长率、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,这是这些细胞发生癌变的标志物,随着暴露于亚背景环境时间的延长,ALP 活性也在增加,这表明了肿瘤的进展。总之,这些数据表明,亚本底辐射照射不会影响 CGL1 细胞的生长、存活或 DNA 损伤,但可能会导致肿瘤转化率的增加,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。
The Role of Natural Background Radiation in Maintaining Genomic Stability in the CGL1 Human Hybrid Model System.
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.
期刊介绍:
Radiation Research publishes original articles dealing with radiation effects and related subjects in the areas of physics, chemistry, biology
and medicine, including epidemiology and translational research. The term radiation is used in its broadest sense and includes specifically
ionizing radiation and ultraviolet, visible and infrared light as well as microwaves, ultrasound and heat. Effects may be physical, chemical or
biological. Related subjects include (but are not limited to) dosimetry methods and instrumentation, isotope techniques and studies with
chemical agents contributing to the understanding of radiation effects.