Increased radioresistance at clinical doses: Investigations from the survival perspective

Abstract

AbstractStandard models of radiation action do not accurately describe survival at low clinically relevant X‐ray doses. This was made evident by survival experiments using methods which assayed a precise number of cells. At extremely low doses of X‐rays (<<0.5 Gy) a hypersensitive response exists which results in an inflection in the survival curve describing the response of many cell lines. In the case of sparsely ionizing radiations, this sensitive response is typically followed by an increased resistant response with a further increment in dose, which varies with cell line. This phenomenon may be explained as resistance induced by small doses of radiation. The background of this clinically interesting effect is described, as are methods to measure survival up to doses of ∼4 Gy. Evidence for increased radioresistance is reviewed and then briefly compared with the adaptive response which has been well studied in lymphocytes at still lower doses using endpoints other than survival. Possible implications for clinical treatment are considered. In addition, we summarize our recent studies directed toward understanding the molecular basis of the increased radioresistance using modifiers of radiation response, repair‐deficient cell lines, and radiation of different linear energy transfer (LET). While DNA damage appears to be a possible trigger for the response, the natures of the exact lesion(s) and the molecular response(s) which result remain unknown. © Wiley‐Liss, Inc.