Key Discipline Laboratory of National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, University of South China, Hengyang, Hunan 421001, People's Republic of China.
Health Phys. 2021 May 1;120(5):541-551. doi: 10.1097/HP.0000000000001385.
The impact of long-term low-dose radiation on human health has always been a concern. Long-term low-dose gamma radiation causes cells continuous injury and causes chromosomal mutations to greatly increase the chance of cancer. Because it is significant to identify biomarkers for long-term low-dose gamma radiation, we investigate the influence of low dose rate on the gene expressions in the AHH-1 lymphocytes cell line (AHH-1 cells) for long-term irradiation. Different dose rates (7, 14, 26, 34, and 43 μGy h-1) of irradiation from gamma radiation in uranium tailings powder were used to irradiate AHH-1 lymphocytes. We used flow cytometry to test the apoptosis of AHH-1 lymphocytes at different dose rates and irradiation times (7-84 d). It was found that 14 μGy h-1 is the most sensitive dose rate of AHH-1 lymphocyte irradiation. The 7-, 14-, and 21-d (2.4, 4.8, and 7.2 mGy) irradiation groups were sensitive, and the 84-d (28.8 mGy) irradiation group was insensitive to low dose gamma radiation. Microarray analysis was conducted on the significantly differentially expressed genes (p<0.05) in the 2.4, 4.8, 7.2, and 28.8 mGy irradiation groups. We found that TFRC1, SLC3A2, SLC39A8, FTH1, ACSL4, and GPX4 are significant genes with low-dose radiation and were constituents of the ferroptosis signaling pathway. In the range of 0-4.8 mGy radiation dose, the expressions of these genes were downregulated with increasing radiation dose, while in the range of 4.8-28.8 mGy, its expression increased with increasing radiation dose. RT-PCR and Western blot were used to detect the mRNA and protein expression of these genes. The results were consistent with those from microarray analysis. Our findings indicate that expression of the TFRC, SLC3A2, SLC39A, FTH1, ACSL4, and GPX4 genes is sensitive to low-dose radiation, and they are main members of the ferroptosis signaling pathway. Therefore, there is a very important connection between ferroptosis and low-dose radiation, which has become a hot topic in international research. These results can provide reference to the effect of ferroptosis on human health with low-dose radiation.
长期低剂量辐射对人类健康的影响一直是人们关注的焦点。长期低剂量伽马辐射会导致细胞持续损伤，并使染色体突变的几率大大增加，从而导致癌症。因此，确定长期低剂量伽马辐射的生物标志物具有重要意义。我们研究了低剂量率对铀尾矿粉中伽马辐射长期辐照下 AHH-1 淋巴细胞系（AHH-1 细胞）基因表达的影响。我们使用不同剂量率（7、14、26、34 和 43 μGy h-1）的γ射线辐照 AHH-1 淋巴细胞。我们使用流式细胞术检测不同剂量率和辐照时间（7-84 天）下 AHH-1 淋巴细胞的凋亡情况。结果表明，14 μGy h-1 是 AHH-1 淋巴细胞辐照最敏感的剂量率。2.4、4.8 和 7.2 mGy 照射组的 7、14 和 21 天（2.4、4.8 和 7.2 mGy）照射组敏感，而 28.8 mGy 照射组对低剂量伽马辐射不敏感。对 2.4、4.8、7.2 和 28.8 mGy 照射组中差异表达基因（p<0.05）进行微阵列分析。我们发现 TFRC1、SLC3A2、SLC39A8、FTH1、ACSL4 和 GPX4 是具有低剂量辐射的重要基因，是铁死亡信号通路的组成部分。在 0-4.8 mGy 辐射剂量范围内，随着辐射剂量的增加，这些基因的表达下调，而在 4.8-28.8 mGy 范围内，其表达随着辐射剂量的增加而增加。使用 RT-PCR 和 Western blot 检测这些基因的 mRNA 和蛋白表达。结果与微阵列分析一致。我们的研究结果表明，TFRC、SLC3A2、SLC39A、FTH1、ACSL4 和 GPX4 基因的表达对低剂量辐射敏感，它们是铁死亡信号通路的主要成员。因此，铁死亡与低剂量辐射之间存在着非常重要的联系，这已成为国际研究的热点。这些结果可为低剂量辐射对人类健康的铁死亡效应提供参考。
