Effects of anesthesia-induced modest hypothermia on cellular radiation sensitivity

To assess the mechanisms of modest hypothermia (MH) and its effects on cellular radiation response, a model of anesthesia-induced modest hypothermia (AIMH) in the adult mice and a model of pure MH in the newborn mice were established. The survival rate of lethally irradiated mice was increased to 72% through AIMH before irradiation. Both apoptosis and necrosis of human fetal bone marrow CD34⁺ hematopoietic stem cells cultured under MH were significantly decreased as detected by MTT and flow cytometry, with three-color labeled by PE-CD₃₄ ⁺/ FITC-AnnexinV /7AAD. The survival and proliferation of mouse bone marrow MNC treated with MH after irradiation were also increased. The MH exerted similar protective effects on the leukemia cell lines A20, HL60, K562 to the normal bone marrow cells, but it enhanced the radiation sensitivity of leukemia cell line FBL3 and mouse melanoma B16F10. No effects have been found on the radiation sensitivity of those cells treated with MH before irradiation. The results also showed that MH mediated the effects on radiation sensitivity, in addition to increasing the oxygen tension. These results show different effects of MH on different cells: (i) AIMH exerts a protective effect on the normal hematopoietic stem cells, some leukemia cell lines A20, HL60, K562, and some neoplasma 3LL, LOVO. And MH exhibits a synthetic effect with anesthetic. (ii) MH enhances the radiation sensitivity of another leukemia and neoplasma cell lines FBL3, B16F10 and CT26. Therefore, AIMH has a potential to enhance the effects of radiation-therapy and decrease side effects on some tumors.