Higuchi T, Nakamura T, Uchino H
Cancer Res. 1977 Oct;37(10):3668-71.
In male BALB/c mice, a combination of individually non-lethal doses of 6-mercaptopurine and endotoxin was significantly lethal. In contrast, mice treated with phenobarbital were resistant to this lethal effect. The high levels of thioinosinic acid in mice that were treated with endotoxin contrasted significantly with the levels in phenobarbital-treated mice. On the other hand, the concentration of hypoxanthine was increased by the administration of phenobarbital and decreased by the administration of endotoxin. The sleeping time and levels of pentobarbital hydroxylase found in endotoxin-treated mice were consistent with the lethality and levels of thioinosinic acid. After mice were treated with endotoxin, their sleeping time was prolonged, which agrees with the course of the stimulatory effects of 6-mercaptopurine anabolism. However, there were no significant differences in hypoxanthine-guanine phosphoribosyltransferase. Furthermore, contrary to expectation, there were significant increases in xanthine oxidase after treatment with endotoxin. Thus, the metabolism of 6-mercaptopurine might be modified by hepatic microsomal enzyme activity.
在雄性BALB/c小鼠中，单独使用无致死剂量的6-巯基嘌呤和内毒素联合使用时具有显著的致死性。相比之下，用苯巴比妥处理的小鼠对这种致死效应具有抗性。内毒素处理的小鼠中硫代次黄苷酸的高水平与苯巴比妥处理的小鼠中的水平形成显著对比。另一方面，苯巴比妥的给药会使次黄嘌呤浓度升高，而内毒素的给药会使其降低。在内毒素处理的小鼠中发现的戊巴比妥羟化酶的睡眠时间和水平与硫代次黄苷酸的致死性和水平一致。小鼠经内毒素处理后，睡眠时间延长，这与6-巯基嘌呤合成代谢的刺激作用过程相符。然而，次黄嘌呤-鸟嘌呤磷酸核糖转移酶没有显著差异。此外，与预期相反，内毒素处理后黄嘌呤氧化酶显著增加。因此，6-巯基嘌呤的代谢可能会被肝微粒体酶活性改变。
