SENSITIVITY OF HUMAN PROSTATIC CARCINOMA CELL LINES TO LOW DOSE RATE RADIATION EXPOSURE

Abstract

Purpose Low dose rate radioemitters, such as 125 I, 103 Pd, and sup 89 Sr, 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 G 1/S and G 2/M transition points. Cancer cells are typically quite sensitive to radiation killing late in the G 2 phase of the replicative cell cycle. Furthermore, most cancer cells accumulating at the G 2/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 effects 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 cytotoxicity 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 G 1/S and the G 2/M cell cycle transition points. For DU 145, PC-3, PPC-1, and TSU-Pr1 cells, treatment with low dose rate radiation triggered G 2/M cell cycle arrest, but not G 1/S arrest. Unexpectedly, the cell cycle redistribution pattern phenotypes observed, G 1/S and G 2/M cell cycle arrest versus G 2/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 pertubations in replicative cell cycle progression were not dominant determinants of low dose rate radiation killing efficacy in human prostate cancer cell lines in vitro.