Howe, O., O'Malley, K., Lavin, M., Gardner, R. A., Seymour, C., Lyng, F., Mulvin, D., Quinlan, D. M. and Mothersill, C. Cell Death Mechanisms Associated with G₂ Radiosensitivity in Patients with Prostate Cancer and Benign Prostatic Hyperplasia. Radiat. Res. 164, 627–634 (2005).

Cells respond to genotoxic insults such as ionizing radiation by halting in the G₂ phase of the cell cycle. Delayed cell death (mitotic death) can occur when the cell is released from G₂, and specific spindle defects form endopolyploid cells (endoreduplication/tetraploidy). Enhanced G₂ chromosomal radiosensitivity has been observed in many cancers and genomic instability syndromes, and it is manifested by radiation-induced chromatid aberrations observed in lymphocytes of patients. Here we compare the G₂ chromosomal radiosensitivity in prostate patients with benign prostatic hyperplasia (BPH) or prostate cancer with disease-free controls. We also investigated whether there is a correlation between G₂ chromosomal radiosensitivity and aneuploidy (tetraploidy and endoreduplication), which are indicative of mitotic cell death. The G₂ assay was carried out on all human blood samples. Metaphase analysis was conducted on the harvested chromosomes by counting the number of aberrations and the mitotic errors (endoreduplication/tetraploidy) separately per 100 metaphases. A total of 1/14 of the controls were radiosensitive in G₂ compared to 6/15 of the BPH patients and 15/17 of the prostate cancer patients. Radiation-induced mitotic inhibition was assessed to determine the efficacy of G₂ checkpoint control in the prostate patients. There was no significant correlation of G₂ radiosensitivity scores and mitotic inhibition in BPH patients (P = 0.057), in contrast to prostate cancer patients, who showed a small but significant positive correlation (P = 0.029). Furthermore, there was no significant correlation between G₂ radiosensitivity scores of BPH patients and endoreduplication/ tetraploidy (P = 0.136), which contrasted with an extremely significant correlation observed in prostate cancer patients (P < 0.0001). In conclusion, cells from prostate cancer patients show increased sensitivity to the induction of G₂ aberrations from ionizing radiation exposure but paradoxically show reduced mitotic indices and aneuploidy as a function of aberration frequency.