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镭-226慢性低剂量/低剂量率高传能线密度照射对人结肠癌细胞系的影响

Influence of chronic low-dose/dose-rate high-LET irradiation from radium-226 in a human colorectal carcinoma cell line.

作者信息

Vo Nguyen T K, Sokeechand Bibi S H, Seymour Colin B, Mothersill Carmel E

机构信息

Radiation Sciences Program, School of Graduate and Postdoctoral Studies, McMaster University, Hamilton, ON, Canada.

Radiation Sciences Program, School of Graduate and Postdoctoral Studies, McMaster University, Hamilton, ON, Canada.

出版信息

Environ Res. 2017 Jul;156:697-704. doi: 10.1016/j.envres.2017.04.041. Epub 2017 May 5.

Abstract

PURPOSE

To evaluate potential damages of chronic environmentally relevant low-dose/dose-rate high-LET irradiation from a naturally occurring alpha-emitting radionuclide (radium-226, Ra) on a human colorectal carcinoma HCT116 p53 cell line.

METHODS

Clonogenic survival assays and mitochondrial membrane potential (MMP) measurement with a sensitive fluorescent MMP probe JC-1 were performed in HCT116 p53 cells chronically exposure to low doses/dose rates of Ra with high-LET. Comparisons were made with the human non-transformed keratinocyte HaCaT cell line and acute low-dose direct low-LET gamma radiation.

RESULTS AND CONCLUSION

The chronic low-dose/dose-rate alpha radiation (CLD/DRAR) did not reduce the clonogenic survival of HCT116 p53 cells over the period of 70 days of exposure. Only one significant reduction in the HCT116 p53 cells' clonogenic survival was when cells were grown with 10,000mBq/mL Ra for 40 days and progeny cells were clonogenically assessed in the presence of 10,000mBq/mL Ra. The cumulative doses that cells received during this period ranged from 0.05 to 46.2mGy. The mitochondrial membrane potential (MMP) dropped initially in both HCT116 p53 and HaCaT cells in response to CLD/DRAR. The MMP in HCT116 p53 cells recovered more quickly at all dose points than and that in HaCaT cells until the end of the exposure period. The highest dose rate of 0.66mGy/day depolarized the HaCaT's mitochondria more consistently during the exposure period. The faster recovery status of the MMP in HCT116 p53 cells than that in HaCaT cells was also observed after exposure to acute low-dose gamma rays. Overall, it was found that CLD/DRAR had little impact on the MMP of human colorectal cancer and keratinocyte cell lines.

摘要

目的

评估天然存在的发射α粒子的放射性核素(镭 - 226,Ra)产生的与环境相关的慢性低剂量/低剂量率高传能线密度辐射对人结肠癌细胞系HCT116 p53的潜在损害。

方法

使用敏感的荧光线粒体膜电位(MMP)探针JC - 1对长期暴露于低剂量/低剂量率高传能线密度Ra的HCT116 p53细胞进行克隆形成存活分析和线粒体膜电位测量。将其与人类未转化的角质形成细胞系HaCaT以及急性低剂量直接低传能线密度γ辐射进行比较。

结果与结论

在70天的暴露期内,慢性低剂量/低剂量率α辐射(CLD/DRAR)并未降低HCT116 p53细胞的克隆形成存活率。仅在细胞与10000mBq/mL Ra一起培养40天,然后在10000mBq/mL Ra存在下对后代细胞进行克隆形成评估时,HCT116 p53细胞克隆形成存活率出现一次显著降低。在此期间细胞接受的累积剂量范围为0.05至46.2mGy。响应CLD/DRAR时,HCT116 p53和HaCaT细胞中的线粒体膜电位(MMP)最初均下降。在暴露期结束前所有剂量点,HCT116 p53细胞中的MMP恢复速度均比HaCaT细胞更快。最高剂量率为0.66mGy/天时,在暴露期内HaCaT细胞的线粒体去极化更为一致。暴露于急性低剂量γ射线后,也观察到HCT116 p53细胞中MMP的恢复状态比HaCaT细胞更快。总体而言发现,CLD/DRAR对人结肠癌细胞系和角质形成细胞系的MMP影响很小。

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