Oligoelements Se, Zn, Mn Plus Lachesis Muta as Radioprotectors of Normal Tissues and Radiosensitizers of Malignant Cells

The in vitro effect of O-LM on radiosensitivity of different human cell lines and the in vivo tolerance to high doses of ionizing radiation induced by the combination of Se, Zn and Mn plus Lachesis muta (O-LM) was evaluated. Sprague-Dawley rats received whole-body irradiation with a single dose (2 to 15 Gy) employing a Cs source of 189 TBq (7.7 Gy/min). A half of rats received daily sc O-LM starting 10 days before irradiation. These animals receiving 8, 10, and 12 Gy showed significantly higher survival versus controls (p<0.0001, 0.003 and 0.0083, respectively). LD50 value for O-LM treated rats was 9.6 Gy vs. 5.8 Gy for controls (p<0.0001). The protective effect of O-LM was also in vivo evaluated on small intestine and bone marrow of nude mice irradiated with a single whole-body dose of 10 Gy. Mice were sacrificed 5 days after irradiation. Mice receiving sc daily O-LM starting 90 days before irradiation, showed better villous and crypts conservation, lack of oedema and vascular damage in comparison to controls. Bone marrows of treated animals showed grade I-II aplasia instead of grade III aplasia in control ones. For in vitro studies, MDA-231 cells (human breast carcinoma) and HBL-100 (normal mammary epithelium) were irradiated with 0-10 Gy employing the same source. Cell cultures were treated with O-LM for 24 hs previous and up to 24 hs post-irradiation. Number of colonies over 50 cells where counted after 10 days. Cell surviving curves indicated that O-LM produced a significant decrease (p<0.001) in survival of transformed cells while no difference was observed in normal HBL-100. These results demonstrated a protective effect on normal tissues exerted by O-LM for in vivo high doses of ionizing irradiation and a significant increase in radiosensitivity on the transformed MDA-231 cells but not in normal HBL-100 cells.