Background/Objective: In this study, for the first time, we examined and compared the sensitivity of four patient-derived cutaneous melanoma cell lines to alpha radiation in vitro and analyzed it in view of cell nucleus area and the formation of double-strand breaks (DSB). Melanoma cells sensitivity to alpha radiation was compared to photon radiation effects. Furthermore, we compared the sensitivity of the melanoma cells to squamous cell carcinoma.Methods:Human melanoma cell lines YDFR.C, DP.C, M12.C, and M16.C, and the squamous cell carcinoma cell line, CAL 27, were irradiated in vitro using Americium-241 as alpha-particle source. Cells were irradiated with doses of 0 to 2.8 gray (Gy). Cell viability, DNA DSB, and nuclear size were measured.Results:1. Alpha radiation caused death and proliferation arrest of all four melanoma cell lines, but inter-tumor heterogeneity was observed. 2. The most sensitive cell line (DP.C) had a significantly larger nucleus area (408 µm2) and the highest mean number of DSB per cell (9.61) compared to more resistant cells. 3. The most resistant cell, M16.C, had a much lower nucleus area (236.99 µm2) and DSB per cell (6.9). 4. Alpha radiation was more lethal than photon radiation for all melanoma cells. 5. The SCC cell, CAL 27, was more sensitive to alpha radiation than all melanoma cells but had a similar number of DSB (6.67) and nucleus size (175.49 µm2) as the more resistant cells. 6. The cytotoxic effect of alpha radiation was not affected by proliferation arrest after serum starvation. 7. Killing of cells by alpha radiation was marginally elevated by ATR or topoisomerase 1 inhibition.Conclusions: This study demonstrates that various human melanoma cells can be killed by alpha radiation but exhibit variance in sensitivity to alpha radiation. Alpha radiation applied using the Intra-tumoral Diffusing alpha-emitters Radiation Therapy (Alpha DaRT) methodology may serve as an efficient treatment for human melanoma.
背景/目的：本研究首次在体外检测并比较了四种患者来源的皮肤黑色素瘤细胞系对α辐射的敏感性，并从细胞核面积及DNA双链断裂（DSB）形成的角度进行分析。同时将黑色素瘤细胞对α辐射的敏感性与光子辐射效应进行对比，并进一步比较了黑色素瘤细胞与鳞状细胞癌细胞的辐射敏感性差异。 方法：采用镅-241作为α粒子源，在体外对人源黑色素瘤细胞系YDFR.C、DP.C、M12.C、M16.C及鳞状细胞癌细胞系CAL 27进行辐照处理，辐射剂量范围为0至2.8戈瑞（Gy）。检测指标包括细胞活力、DNA双链断裂情况及细胞核尺寸。 结果：1. α辐射可导致所有四种黑色素瘤细胞系死亡并抑制其增殖，但观察到明显的肿瘤间异质性；2. 最敏感的细胞系（DP.C）具有显著更大的细胞核面积（408 µm²）及最高的平均单细胞DSB数量（9.61）；3. 最具抗性的M16.C细胞则表现出更小的细胞核面积（236.99 µm²）和更低的单细胞DSB数量（6.9）；4. 相较于光子辐射，α辐射对所有黑色素瘤细胞均表现出更强的杀伤效力；5. 鳞状细胞癌细胞CAL 27对α辐射的敏感性高于所有黑色素瘤细胞，但其DSB数量（6.67）和细胞核尺寸（175.49 µm²）与抗性较强的黑色素瘤细胞相近；6. 血清饥饿诱导的增殖停滞未影响α辐射的细胞毒性效应；7. 抑制ATR或拓扑异构酶1仅轻微增强α辐射对细胞的杀伤作用。 结论：本研究证实α辐射可有效杀伤多种人源黑色素瘤细胞，但其敏感性存在显著差异。采用瘤内扩散α发射体放射治疗（Alpha DaRT）技术实施的α辐射可能成为治疗人类黑色素瘤的有效方法。
肿瘤(癌症)患者之家