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Carbon ion radiotherapy has the advantages of better therapeutic effect and fewer side effects compared with those of X-rays in many kinds of tumors, including prostate cancer, and thus is an attractive treatment approach for prostate cancer. However, the biological effects and underlying mechanisms of carbon ion irradia-tion in prostate cancer are not yet fully understood. Therefore, this study systematically compared the effects of carbon ion irradiation with those of X-ray irradiation onDNA damage response and found that carbon ion irradia-tion was more effective than X-ray irradiation. Carbon ion irradiation can induce a high level of DNA double-strand break damage, reflected by the number of c-H2A histone family member X foci, as well as by the foci lasting time and size. Moreover, carbon ion irradiation exhibited strong and long-lasting inhibitory effect on cell survival capabil-ity, induced prolonged cell cycle arrest, and increased apoptosis in PC-3 cells. As an underlying mechanism, we speculated that carbon ion irradiation-induced DNA dam-age evokes cell cycle arrest and apoptosis via the pRb/E2F1/c-Myc signaling pathway to enhance the radiosensi-tivity of p53-deficient prostate cancer PC-3 cells. Collec-tively, the present study suggests that carbon ion irradiation is more efficient than X-ray irradiation and may help to understand the effects of different radiation qualities on the survival potential of p53-deficient prostate cancer cells.