Cell death mechanisms associated with G(2) radiosensitivity in patients with prostate cancer and benign prostatic hyperplasia

Howe, O., OMalley, K., Lavin, M., Gardner, R. A., Seymour, C., Lyng, F., Mulvin, D., Quinlan, D. M. and Mothersill, C. (2005) Cell death mechanisms associated with G(2) radiosensitivity in patients with prostate cancer and benign prostatic hyperplasia. Radiation Research, 164 5: 627-634. doi:10.1667/RR3454.1


Author Howe, O.
OMalley, K.
Lavin, M.
Gardner, R. A.
Seymour, C.
Lyng, F.
Mulvin, D.
Quinlan, D. M.
Mothersill, C.
Title Cell death mechanisms associated with G(2) radiosensitivity in patients with prostate cancer and benign prostatic hyperplasia
Journal name Radiation Research   Check publisher's open access policy
ISSN 0033-7587
Publication date 2005-01-01
Sub-type Article (original research)
DOI 10.1667/RR3454.1
Volume 164
Issue 5
Start page 627
End page 634
Total pages 8
Place of publication Oak Brook
Publisher Radiation Research Soc
Collection year 2005
Language eng
Subject C1
Abstract Cells respond to genotoxic insults such as ionizing radiation by halting in the G(2) phase of the cell cycle. Delayed cell death (mitotic death) can occur when the cell is released from G(2), and specific spindle defects form endopolyploid cells (endoreduplication/tetraploidy). Enhanced G(2) 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 G(2) 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 G(2) chromosomal radiosensitivity and aneuploidy (tetraploidy and endoreduplication), which are indicative of mitotic cell death. The G(2) 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 G(2) 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 G(2) checkpoint control in the prostate patients. There was no significant correlation of G(2) 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 G(2) 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 G(2) aberrations from ionizing radiation exposure but paradoxically show reduced mitotic indices and aneuploidy as a function of aberration frequency.
Keyword Biology
Biophysics
Radiology, Nuclear Medicine & Medical Imaging
Double-strand Breaks
Chromosomal Radiosensitivity
Genetic Predisposition
Dna-repair
Spindle Disruption
Tetraploid State
Mammalian-cells
Arrest
Damage
Apoptosis
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2006 Higher Education Research Data Collection
School of Medicine Publications
 
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