Melanoma Cells from Different Patients Differ in Their Sensitivity to Alpha Radiation-Mediated Killing, Sensitivity Which Correlates with Cell Nuclei Area and Double Strand Breaks

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.