Investigation of hypersensitivity to fractionated low-dose radiation exposure

Purpose: Hypersensitivity to cell killing of exponentially growing cells ex posed to X-rays and gamma rays has been reported for doses below about 0.5 Gy. The reported results have been interpreted to suggest that a dose of 0. 5 Gy or less is not sufficient to trigger an inducible repair mechanism. Th e purpose of this study was to examine this suggested hypersensitivity afte r multiple low doses (0.3 Gy) of gamma rays where a) the effect would be ex pected to be significantly magnified, and b) the effect might be of clinica l relevance. Methods and Materials: C3H 10T 1/2 mouse embryo cells were grown to conflue nce in culture vessels. While in plateau phase of growth, cells were expose d to 6 Gy of gamma rays, delivered in either 6 Gy, 3 Gy, 2 Gy, 1 Gy or 0.3 Gy well-separated fractions. Corresponding experiments were performed with V-79 and C3H 10T 1/2 cells in exponential growth, Cells were replated at lo w density and assayed for clonogenicity. Results: The results of this study were not inconsistent with some hypersen sitivity at low doses, in that 20 fractions each of 0.3 Gy produced a sligh tly lower (though nonsignificant) surviving fraction compared with the same dose given in 2-Gy fractions. However, the results of the 20 x 0.3 GS expo sures also agreed well with the standard linear-quadratic (LQ) model predic tions based on high dose per fraction (1-6 Gy) data. In addition, effects o f cellular redistribution were seen which were explained quantitatively wit h an extended version of the LQ model. Conclusions: These experiments were specifically designed to magnify and pr obe possible clinical implications of proposed "low-dose hypersensitivity" effects, in which significant deviations at low doses from the LQ model hav e been suggested. In fact, the results at low doses per fraction were consi stent with LQ predictions based on higher dose per fraction data. This find ing is in agreement with the well-documented utility of the LQ approach in estimating isoeffect doses for alternative fractionation schemes, and for b rachytherapy. (C) 1999 Elsevier Science Inc.