Koch C J, Howell R L, Biaglow J E
Br J Cancer. 1979 Mar;39(3):321-9. doi: 10.1038/bjc.1979.56.
The nitro-aromatic radiosensitizing drugs are selectively toxic to hypoxic mammalian cells, and this toxicity can be greatly increased by the addition of ascorbate. The ascorbate itself is not toxic to either hypoxic or aerobic cells (as long as catalase is present to prevent the formation of significant concentrations of hydrogen peroxide) and the mixture of ascorbate plus radiosensitizer is not more toxic to aerobic cells. Sulphydryl reducing agents and dithionite have an effect opposite to ascorbate and decrease the toxicity of nitro-aromatic drugs under hypoxic conditions. Sulphydryl reducing agents are also reported to nullify the radiosensitizing properties of nitro-aromatic drugs, in contrast to ascorbate which has no effect on the radiosensitizing properties. The toxicity of nitro-aromatic drugs decreases rapidly with increasing O2 concentration. This decrease is much less rapid when ascorbate is present. The role of ascorbate in this case may be primarily as an O2 scavenger, although it is also possible that the toxic species produced by radiosensitizer-ascorbate mixtures is less easily removed or detoxified by O2.
硝基芳香族放射增敏药物对缺氧的哺乳动物细胞具有选择性毒性，加入抗坏血酸盐可大大增强这种毒性。抗坏血酸盐本身对缺氧或需氧细胞均无毒（只要有过氧化氢酶存在以防止形成高浓度的过氧化氢），且抗坏血酸盐加放射增敏剂的混合物对需氧细胞的毒性并不更强。巯基还原剂和连二亚硫酸盐具有与抗坏血酸盐相反的作用，在缺氧条件下会降低硝基芳香族药物的毒性。据报道，巯基还原剂也会消除硝基芳香族药物的放射增敏特性，而抗坏血酸盐对放射增敏特性没有影响。硝基芳香族药物的毒性会随着氧气浓度的增加而迅速降低。当存在抗坏血酸盐时，这种降低的速度要慢得多。在这种情况下，抗坏血酸盐的作用可能主要是作为一种氧气清除剂，尽管也有可能是放射增敏剂 - 抗坏血酸盐混合物产生的有毒物质不太容易被氧气清除或解毒。
