Dempke W, Nehls P, Wandl U, Soll D, Schmidt C G, Osieka R
J Cancer Res Clin Oncol. 1987;113(4):387-91. doi: 10.1007/BF00397725.
Cells from a resistant ("Gr II") and a sensitive ("Str") human melanoma xenograft were incubated in vitro with O6-methylguanine for 2 h, subsequently treated with 1-(2-chloroethyl)-1-nitroso-3(4-methyl)-cyclohexylurea (MeCCNU) for 1 h and then plated in soft agar. In the resistant cells the O6-methylguanine pretreatment (2 mM) yielded an increase in sensitivity towards MeCCNU by a factor of 7.5. In the sensitive melanoma cells pretreatment with O6-methylguanine did not increase cytotoxicity. Human bone marrow cells from three normal donors were similarly pretreated with O6-methylguanine and MeCCNU. There was a clear increase in MeCCNU-induced cytotoxicity. We conclude, that while O6-methylguanine does potentiate the action of MeCCNU in resistant melanoma cells, the therapeutic usefulness of this treatment strategy may be limited.
将来自抗药（“Gr II”）和敏感（“Str”）人黑色素瘤异种移植瘤的细胞在体外与O6-甲基鸟嘌呤孵育2小时，随后用1-(2-氯乙基)-1-亚硝基-3(4-甲基)-环己基脲（甲环亚硝脲，MeCCNU）处理1小时，然后接种于软琼脂中。在抗药细胞中，O6-甲基鸟嘌呤预处理（2 mM）使对MeCCNU的敏感性增加了7.5倍。在敏感的黑色素瘤细胞中，用O6-甲基鸟嘌呤预处理并未增加细胞毒性。来自三名正常供体的人骨髓细胞同样用O6-甲基鸟嘌呤和MeCCNU进行预处理。MeCCNU诱导的细胞毒性明显增加。我们得出结论，虽然O6-甲基鸟嘌呤确实能增强MeCCNU在抗药黑色素瘤细胞中的作用，但这种治疗策略的治疗效用可能有限。
