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.

中文翻译：

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与低剂量辐射相关的 AHH-1 淋巴细胞中铁死亡生物标志物的鉴定。

长期低剂量辐射对人体健康的影响一直备受关注。长期低剂量伽马射线导致细胞持续损伤，导致染色体突变，大大增加患癌症的机会。由于识别长期低剂量伽玛射线的生物标志物具有重要意义，因此我们研究了低剂量率对长期照射的AHH-1淋巴细胞系（AHH-1细胞）基因表达的影响。采用不同剂量率（7、14、26、34、43μGy·h-1）的铀尾矿粉伽马射线照射AHH-1淋巴细胞。我们采用流式细胞术检测不同剂量率和照射时间（7-84 d）下AHH-1淋巴细胞的凋亡情况。结果发现14 μGy h-1是AHH-1淋巴细胞照射最敏感的剂量率。7、14和21天（2.4、4.8和7.2 mGy）照射组对低剂量伽马射线敏感，84天（28.8 mGy）照射组对低剂量伽马射线不敏感。对2.4、4.8、7.2和28.8 mGy照射组中显着差异表达的基因（p<0.05）进行微阵列分析。我们发现TFRC1、SLC3A2、SLC39A8、FTH1、ACSL4和GPX4是低剂量辐射的重要基因，并且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，这些基因的表达量随着辐射剂量的增加而下调，而在4.8-28.8 mGy范围内，其表达量随着辐射剂量的增加而增加。RT-PCR和Western blot检测这些基因的mRNA和蛋白表达。结果与微阵列分析的结果一致。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非常重要的联系，已成为国际研究的热点。这些结果可为低剂量辐射铁死亡对人体健康的影响提供参考。