Rojas A, Stewart F A, Denekamp J
Br J Cancer. 1982 May;45(5):684-93. doi: 10.1038/bjc.1982.109.
We have studied the radiomodifying action in mouse skin of WR-2721 and misonidazole (MISO) when used alone or in combination. The radioprotection with WR-2721 was drug-dose dependent and highly influenced by the O2 concentration at the time of irradiation. Significant sensitizaton was observed with MISO, especially in air-breathing mice. The combination of WR-2721 and MISO produced a radiation response intermediate between the resistant and sensitive responses to either drug alone. The precise degree of sensitivity was dependent on the relative doses of protector and sensitizer. We have also studied the interaction of both drugs in terms of drug-induced lethality, which showed a clear toxic interaction. The WR-2721 LD50 was reduced by a factor of 1.4 with only 200 mg/kg of MISO. We conclude that the combination of WR-2721 and MISO shows an interaction in terms of drug toxicity and radiation response, such that the radioprotection of skin is reduced or even abolished with low doses of MISO.
我们研究了WR-2721和米索硝唑（MISO）单独使用或联合使用时对小鼠皮肤的辐射修饰作用。WR-2721的辐射防护作用具有药物剂量依赖性，并且在照射时受氧气浓度的影响很大。观察到MISO具有显著的增敏作用，尤其是在呼吸空气的小鼠中。WR-2721和MISO联合使用产生的辐射反应介于单独使用任何一种药物时的抗性和敏感反应之间。精确的敏感程度取决于保护剂和增敏剂的相对剂量。我们还研究了两种药物在药物诱导的致死性方面的相互作用，结果显示出明显的毒性相互作用。仅200mg/kg的MISO就能使WR-2721的半数致死剂量（LD50）降低1.4倍。我们得出结论，WR-2721和MISO联合使用在药物毒性和辐射反应方面表现出相互作用，以至于低剂量的MISO会降低甚至消除皮肤的辐射防护作用。
