Ling L L, Streffer C, Sutherland R
Int J Radiat Oncol Biol Phys. 1986 Jul;12(7):1231-4. doi: 10.1016/0360-3016(86)90265-8.
The modulation of the hypoxic toxicity and binding of Misonidazole (MISO) by glucose and lactate was studied by exposing exponential EMT6/Ro cells to 5 mM MISO under hypoxic conditions. The concentrations of glucose used were 0.015 mM and 5 mM, and the concentrations of lactate were 0, 3 and 10 mM. There was no significant hypoxic toxicity due to MISO in the absence of glucose. However, with 5 mM glucose, after a latent period of 0.5 hours, there was a rapid decrease in cell survival to less than 0.1% at 2.5 hours incubation in 5 mM MISO. The binding of MISO was also increased by glucose. The amount of MISO bound to cells in 0.015 mM glucose leveled off at 2 nmoles MISO/7 X 10(5) cells at 1 hour, whereas the binding in 5 mM glucose continued to increase to more than 5 nmoles MISO/7 X 10(5) cells after 3 hours incubation. There was no detectable effect of lactate on the binding of MISO to the cells either in 0.015 mM or 5 mM glucose. The high affinity of this binding was indicated by the lack of exchange of radioactive MISO with non-radioactive MISO even after 2 hours of incubation. These data showed that glucose concentrations could modify the toxicity and binding of MISO to hypoxic cells.
通过在缺氧条件下将指数生长的EMT6/Ro细胞暴露于5 mM米索硝唑（MISO）中，研究了葡萄糖和乳酸对MISO缺氧毒性及结合的调节作用。所用葡萄糖浓度为0.015 mM和5 mM，乳酸浓度为0、3和10 mM。在无葡萄糖时，MISO无明显缺氧毒性。然而，在5 mM葡萄糖存在下，经过0.5小时的潜伏期后，在5 mM MISO中孵育2.5小时时，细胞存活率迅速下降至低于0.1%。葡萄糖也增加了MISO的结合。在0.015 mM葡萄糖中，与细胞结合的MISO量在1小时时稳定在2 nmol MISO/7×10⁵个细胞，而在5 mM葡萄糖中孵育3小时后，结合量继续增加至超过5 nmol MISO/7×10⁵个细胞。无论是在0.015 mM还是5 mM葡萄糖中，乳酸对MISO与细胞的结合均无明显影响。即使孵育2小时后，放射性MISO与非放射性MISO之间也缺乏交换，这表明这种结合具有高亲和力。这些数据表明，葡萄糖浓度可改变MISO对缺氧细胞的毒性和结合。
