The cytotoxicity of decays of tritium and iodine-125 incorporated in DNA of mammalian cells. Implications for the low-LET dosimetry of incorporated nuclides.

To quantify the toxicity of low-LET radiation from incorporated radionuclides, we have determined the toxicity of decays of [3H]dThd pulse-incorporated into CHO cells in early S phase, with the cells frozen for decay accumulation at 30, 120 or 360 min after the pulse. D37 values of 1500, 2000 and 2100 decays were found by colony formation assay, corresponding to average nuclear doses of 4.6 and 2.7 Gy at the 30- and 360-min times. As D37 for external irradiation (60Co, 2.2 Gy/min) under these conditions is approximately 18 Gy, these results confirm the inadequacy of the dosimetry used for external irradiation to predict the biological effects of the low-LET radiation from incorporated radionuclides. We also determined the toxicity of 125IdU administered as above, and have confirmed the previously reported finding that D37 falls dramatically from 165 decays at 30 min to 40 decays at 360 min. Using the data for tritium to estimate the effect of the dose of 125I low-LET radiation, we conclude that even at 30 min, most of the toxicity of the 125I decays is due to the high-LET portion of the 125I electron spectrum, not the low-LET portion as reported previously.