Chromosome Damage and Cell Proliferation Rates in In Vitro Irradiated Whole Blood as Markers of Late Radiation Toxicity After Radiation Therapy to the Prostate

• Published in: International journal of radiation oncology, biology, physics Vol. 85; no. 5; pp. 1346 - 1352
• Main Authors: Beaton, Lindsay A., MSc, Ferrarotto, Catherine, MLT, Marro, Leonora, MSc, Samiee, Sara, MD, Malone, Shawn, MD, Grimes, Scott, Malone, Kyle, Wilkins, Ruth C., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2013
• Subjects: Aged; ANDROGENS; ANIMAL TISSUES; CELL PROLIFERATION; Cell Proliferation - radiation effects; CHROMOSOMAL ABERRATIONS; Chromosome Aberrations; DICENTRIC CHROMOSOMES; Genetic Markers - genetics; Hematology, Oncology and Palliative Medicine; Humans; IN VITRO; IRRADIATION; LYMPHOCYTES; Lymphocytes - pathology; Lymphocytes - radiation effects; Male; Metaphase - genetics; Middle Aged; MITOSIS; NEOPLASMS; PATIENTS; PROCTITIS; Proctitis - blood; Proctitis - etiology; Prospective Studies; PROSTATE; Prostatic Neoplasms - blood; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; Radiation Dosage; Radiation Injuries - genetics; Radiation Injuries - pathology; Radiation Tolerance - genetics; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; TOXICITY
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2012.09.026

Purpose In vitro irradiated blood samples from prostate cancer patients showing late normal tissue damage were examined for lymphocyte response by measuring chromosomal aberrations and proliferation rate. Methods and Materials Patients were selected from a randomized trial evaluating the optimal timing of dose-escalated radiation and short-course androgen deprivation therapy. Of 438 patients, 3% experienced grade 3 late radiation proctitis and were considered to be radiosensitive. Blood samples were taken from 10 of these patients along with 20 matched samples from patients with grade 0 proctitis. The samples were irradiated at 6 Gy and, along with control samples, were analyzed for dicentric chromosomes and excess fragments per cell. Cells in first and second metaphase were also enumerated to determine the lymphocyte proliferation rate. Results At 6 Gy, there were statistically significant differences between the radiosensitive and control cohorts for 3 endpoints: the mean number of dicentric chromosomes per cell (3.26 ± 0.31, 2.91 ± 0.32; P =.0258), the mean number of excess fragments per cell (2.27 ± 0.23, 1.43 ± 0.37; P <.0001), and the proportion of cells in second metaphase (0.27 ± 0.10, 0.46 ± 0.09; P =.0007). Conclusions These results may be a valuable indicator for identifying radiosensitive patients and for tailoring radiation therapy.