Sensitivity of human prostatic carcinoma cell lines to low dose rate radiation exposure

Purpose: Low dose rate radioemitters, such as ¹²⁵I, ¹⁰³Pd, and ⁸⁹Sr, have been used both for local and systemic treatment of prostate cancer. Most normal cells exposed to ionizing radiation characteristically activate cell cycle checkpoints, resulting in cell cycle arrest at the G₁/S and G₂/M transition points. Cancer cell are typically quite sensitive to radiation killing late in the G₂ phase of the replicative cell cycle. Furthermore, most cancer cells accumulating at the G₂/M transition point as a result of low dose rate radiation exposure appear to become sensitive to further low dose rate irradiation. For this reason, protracted exposure of cancer cells to low dose rate radiation has been proposed to result in increased cancer cell killing as compared with brief exposures of cancer cells to high dose rate radiation. Since many human prostatic carcinomas contain somatic genome alterations targeting genes which affect the cell cycle and radiation-associated cell cycle checkpoints, we evaluated the effect of low dose rate radiation exposure on the cell cycle and on clonogenic survival for various human prostatic carcinoma cell lines. Materials and Methods: Human prostatic carcinoma cells from the LNCaP, DU 145, PC-3, PPC-1, and TSU-Pr1 cell lines were exposed to low dose rate (0.25 Gy/hour) or high dose rate (60 Gy/hour) radiation in vitro and then assessed for radiation cyclototoxicty by clonogenic survival assay. Cell cycle perturbations following protracted exposure to low dose rate radiation were evaluated using flow cytometry. Results: For LNCaP cells, low dose rate radiation exposure resulted in an accumulation of cells at both the G₁/S and the G₂/M cell cycle transition points. For DU 145, PC-3, PPC-1, and TSU-Pr1 cells, treatment with low dose rate radiation triggered G₂/M cell cycle arrest, but not G₁/S arrest. Unexpectedly, the cell cycle redistribution pattern phenotypes observed, G₁/S and G₂/M cell cycle arrest versus G₂/M arrest alone, appeared to have little effect on low dose rate radiation survival. Furthermore, while PC-3, PPC-1, and TSU-Pr1 cells exhibited increased cytotoxic sensitivity to low dose rate versus fractionated high dose rate radiation treatment, DU 145 and LNCaP cells did not. Conclusions: Radiation-associated perturbations in replicative cell cycle progression were not dominant determinants of low dose rate radiation killing efficacy in human prostate cancer cell lines in vitro.