INDIVIDUAL RADIOSENSITIVITY AND ITS RELEVANCE TO HEALTH PHYSICS

Dose-Response: An International Journal Volume 5 Issue 4 NON-LINEAR RISK FROM LOW DOSE RADIATION EXPOSURE Article 12 12-2007 INDIVIDUAL RADIOSENSITIVITY AND ITS RELEVANCE TO HEALTH PHYSICS Kara Schnarr McMaster University, Hamilton, ON, Canada Ian Dayes Juravinski Cancer Centre, Hamilton, ON, Canada Jinka Sathya Juravinski Cancer Centre, Hamilton, ON, Canada Douglas Boreham McMaster University, Hamilton, ON, Canada Follow this and additional works at: https://scholarworks.umass.edu/dose_response Recommended Citation Schnarr, Kara; Dayes, Ian; Sathya, Jinka; and Boreham, Douglas (2007) "INDIVIDUAL RADIOSENSITIVITY AND ITS RELEVANCE TO HEALTH PHYSICS," Dose-Response: An International Journal: Vol. 5 : Iss. 4 , Article 12. Available at: https://scholarworks.umass.edu/dose_response/vol5/iss4/12 This Article is brought to you for free and open access by ScholarWorks@UMass Amherst. It has been accepted for inclusion in Dose-Response: An International Journal by an authorized editor of ScholarWorks@UMass Amherst. For more information, please contact . Schnarr et al.: Lymphocyte sensitivity and individual variability InternationalDOSE-RESPONSESociety Dose-Response 5:333–348, 2007 Formerly Nonlinearity in Biology, Toxicology, and Medicine Copyright © 2007 University of Massachusetts ISSN: 1559-3258 DOI: 10.2203/dose-response.07-022.Schnarr w w w . D o s e - R e s p o n s e . o r g INDIVIDUAL RADIOSENSITIVITY AND ITS RELEVANCE TO HEALTH PHYSICS Kara Schnarr 䊐 Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada Ian Dayes, Jinka Sathya 䊐 Juravinski Cancer Centre, Hamilton, Ontario, Canada Douglas Boreham 䊐 Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada 䊐 Radiation protection regulations have been established to reduce exposure of individuals to acceptable safe levels. These limits assume that people have similar responses to ionizing radiation and that there is no variation in individual radiation risk. The purpose of this research was to determine if apoptosis in lymphocytes can be used to assess individual sensitivity to ionizing radiation. Blood samples were taken from 54 males ranging in age from 19–85 years. Apoptosis was measured using modified flow cytometry based Annexin-FITC/7AAD and DiOC6/7AAD assays in different populations of lymphocytes (total mixed lymphocyte population, subset CD4+ or CD8+ lymphocytes) after exposure to in vitro doses of 0, 2, 4 or 8Gy (dose rate 0.1Gy/min). The variation in individual responses to radiation was large. The variation was the largest in the CD4+ lymphocyte subpopulation. Radiation-induced apoptosis decreased with age of donor demonstrating that as people age their lymphocytes may become relatively more resistant to radiation. This research shows that individuals have marked differences in their sensitivity to radiation and protection policies may someday need to be tailored for some individuals. Keywords: Lymphocyte sensitivity, Apoptosis, Individual Sensitivity INTRODUCTION In the nuclear power industry and other activities that use ionizing radiation such as medical diagnostics and therapy, limits are set to ensure doses are at a safe level. These limits assume that people have equal responses to ionizing radiation and that there is no variation in radiation risk. However, in radiotherapy, where patients receive large doses of radiation to their tumours and the surrounding tissue volume, it is well documented that all patients do not respond the same to a specific treatment plan. As a result, 5 -10% of patients will have adverse reactions. In other activities that involve exposure to ionizing radiation, individual risk from low doses is extrapolated from risks observed from high dose exposures. However, the actual risk to an individual likely relates to their own intrinsic sensitivity to the radiation. Therefore, experiments that can determine Address correspondence to Douglas Boreham, Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada, L8S4K1. Tel. +1-905-525-9140 ext. 27538; Fax: +1-905-522-5982; e-mail: 333 Published by ScholarWorks@UMass Amherst, 2014 1 Dose-Response: An International Journal, Vol. 5 [2014], Iss. 4, Art. 12 K. Schnarr, I. Dayes, J. Sathya, and D. Boreham the range of individual responses to radiation are useful for a better understanding of actual risk. The ability to predict radiation sensitivity would benefit both medical and health physicists, and emergency responders (Kanda et al, 1999, Kleinerman et al, 2006). If radiation sensitive patients could be identified before they undergo therapy, a reduced dose regiment or alternative therapy could be prescribed (Barber et al, 2000). Furthermore, predicting radiation sensitive individuals would allow the radiation protection industry to tailor dose limits to an individual, reducing risk to the worker. If an individual has a decreased ability to detect damage caused by radiation, perhaps a low dose exposure would not be detected or repaired properly, turning a ‘safe’ exposure into a potential cancer causing event. We postulate that this variation in radiation response is due to the individual’s intrinsic cellular response to the damage created by radiation. These individuals could have altered genetic factors regulating DNA repair processes and/or controlling apoptosis. Therefore, this systemic predisposition results in a lack of ability for damaged cells to be eliminated properly or be repaired and consequently causes an adverse reaction. Understanding this phenomenon is crucial for radiation protection practices, since these radiosensitive individuals may also be at increased risk to high occupational or medical exposures. Recent evidence indicates that some cancer patients that exhibit adverse effects (toxicity) from radiotherapy may also have abnormal apoptotic responses in subpopulations of their lymphocytes. Apoptosis is a form of programmed cell death that is the dominant mode of cell killing induced by radiation in human lymphocytes. Measuring levels of apoptosis in lymphocytes has been suggested as a method for estimating in vivo dose (Menz, 1997; Boreham, 1996) following an accidental exposure to radiation. Menz et al, researched the dose response of human lymphocytes when exposed to doses up to 8Gy of gamma radiation as measured by a flow cytometry apoptosis assay in 5 donors. Boreham et al, (1996) investigated doses of up to 1Gy using the in situ terminal deoxynucleotidyl transferase (TdT) assay and the fluorescence analysis of DNA unwinding (FADU) assay to quantify apoptosis in 10 donors. These studies found that apoptosis was detectable for doses as low as 0.05Gy and reproducible enough to act as a biological dosimeter. The purpose of this study was to assess the feasibility of using apoptosis as an assay to investigate indiv (...truncated)