[Biologic effects of total body irradiation with single dose administered with various dose-rate]

Total body irradiation (TBI) is used in conditioning regimens prior to bone marrow transplantation (BMT) in haematologic diseases to achieve the objective of eradicating bone marrow stem cells. The dose deliverable to the whole body is limited by the radiation tolerance of the normal tissues, especially of the lung, which is the major dose limiting organ because of the high incidence of interstitial pneumonia. The dose rate is important to successfully affect the therapeutic ratio of TBI and BMT; two different dose-rate schedules have been compared to define radiation damages in all tissues. Twenty mini-pigs were lethally irradiated, TBI was performed with 750 cGy total dose, but with two different midplane dose rates: a low dose rate (LDR) of 5 cGy/min and a quite high dose rate (HDR) of 25 cGy/min. In mini-pigs lethally irradiated with HDR, microscopic examination showed severe hemorrhagic changes in bone marrow, lymphonodes, lung parenchyma and other tissues, more prominent than in LDR mini-pigs. Hystologic pictures showed moderate changes in kidney and liver parenchyma, in thyroid and brain tissue both in HDR and in LDR group. Tissue radiation damages are related not only to TBI total dose, but to the dose-rate; the selection of a low dose-rate is useful to reduce radiation cell killing by accumulation of lethal injury to normal tissues, especially to the lung.