Effect of Proton Radiation on DNA Damage in Human Malignant Melanoma A375 Cell

Abstract

Malignant melanoma is a highly invasive skin cancer that can rapidly metastasize and is often resistant to traditional chemotherapy and radiotherapy. In recent years, the incidence and mortality rates of malignant melanoma are increasing, especially among young people. Therefore, there is an increasing need to develop effective therapies for this deadly disease. Proton therapy is a promising cancer treatment that uses protons to target and destroy cancer cells. Compared to traditional radiation therapy, the advantage of proton therapy is that it can provide highly concentrated radiation doses to tumors while minimizing damage to surrounding healthy tissue. However, to fully exploit the potential of proton therapy, it is important to understand the biological effects of proton radiation on cancer cells and normal tissues. In this study, A375 cells were irradiated with 15 MeV protons and γ-ray at different doses (0, 1, 2, 4, and 8 Gy) to investigate the effects of different radiation types and doses on A375 cell survival, cell cycle progression, cell apoptosis, and DNA damage. The results show that as the dose increases from 1 Gy to 8 Gy, the survival rate of A375 cells decreases, and cell survival induced by 4.8 Gy proton radiation is significantly lower than that induced by γ-ray. These findings indicate that proton radiation is more effective in killing cancer cells than traditional radiation therapy. Additionally, the study shows that radiation-induced G2/M phase arrest increases with dose, with proton-induced cell cycle arrest stronger than that induced by γ-ray. Forty-eight hours after irradiation, the cell cycle arrest induced by γ-ray is mostly released, but the cell cycle arrest induced by proton radiation is not completely released at 2.8 Gy except for 1 Gy. This suggests that proton radiation has a more sustained effect on cancer cells, making it a potentially more effective treatment option for malignant melanoma. The study also shows that cell apoptosis induced by ionizing radiation increases with increasing irradiation dose, and the proportion of apoptosis increases with time, with the cell apoptosis rate induced by proton radiation higher than that induced by γ-ray. After irradiation with 2 Gy, the γH2AX focus peaks induced by γ-ray and protons appeares at 1 hour post-irradiation, with the number and size of γH2AX foci induced by proton radiation higher than those induced by γ-ray. These findings suggest that proton radiation induces more DNA damage than traditional radiation therapy, which may explain its increased effectiveness in killing cancer cells. Overall, the results in this paper provide valuable insights into the biological effects of proton radiation on cancer cells and highlight the potential of proton therapy as an effective treatment option for malignant melanoma. The data generated from this study could provide fundamental data for future proton beam therapy and radiobiology studies.

Keywords

• human malignant melanoma a375 cell
• proton radiation
• cell cycle
• cloning rate
• cell apoptosis
• γh2ax focus