Investigation of hypersensitivity to fractionated low-dose radiation exposure.

PURPOSE Hypersensitivity to cell killing of exponentially growing cells exposed 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. The purpose of this study was to examine this suggested hypersensitivity after multiple low doses (0.3 Gy) of gamma rays where a) the effect would be expected to be significantly magnified, and b) the effect might be of clinical relevance. METHODS AND MATERIALS C3H 10T1/2 mouse embryo cells were grown to confluence in culture vessels. While in plateau phase of growth, cells were exposed 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 10T1/2 cells in exponential growth. Cells were replated at low density and assayed for clonogenicity. RESULTS The results of this study were not inconsistent with some hypersensitivity at low doses, in that 20 fractions each of 0.3 Gy produced a slightly lower (though nonsignificant) surviving fraction compared with the same dose given in 2-Gy fractions. However, the results of the 20 x 0.3 Gy exposures also agreed well with the standard linear-quadratic (LQ) model predictions based on high dose per fraction (1-6 Gy) data. In addition, effects of cellular redistribution were seen which were explained quantitatively with an extended version of the LQ model. CONCLUSIONS These experiments were specifically designed to magnify and probe possible clinical implications of proposed "low-dose hypersensitivity" effects, in which significant deviations at low doses from the LQ model have been suggested. In fact, the results at low doses per fraction were consistent with LQ predictions based on higher dose per fraction data. This finding is in agreement with the well-documented utility of the LQ approach in estimating isoeffect doses for alternative fractionation schemes, and for brachytherapy.