用N-甲基-N'-硝基-N-亚硝基胍（MNNG）预处理人肿瘤细胞对米托唑胺的DNA交联作用及细胞毒性的影响。
The effects of pretreatment of human tumour cells with MNNG on the DNA crosslinking and cytotoxicity of mitozolomide.
作者信息
Gibson N W, Erickson L C
出版信息
Br J Cancer. 1985 Aug;52(2):251-8. doi: 10.1038/bjc.1985.185.
Mitozolomide and its decomposition product MCTIC were found to be more cytotoxic to BE colon carcinoma cells in vitro than to HT-29 cells, another colon carcinoma cell line. In addition mitozolomide and MCTIC induced DNA interstrand crosslinks in the BE but not the HT-29 cell line. BE cells are deficient in the repair of O6-methylguanine lesions and are designated Mer-, whereas, HT-29 cells are proficient in this repair process and are designated Mer+. Thus DNA interstrand crosslinking produced by mitozolomide and MCTIC appears to correlate with the Mer phenotype. Pretreatment of HT-29 cells (Mer+) with the DNA methylating agent MNNG allows mitozolomide or MCTIC to produce DNA interstrand crosslinks. HT-29 cells also become more sensitive to the cell killing of mitozolomide and MCTIC with MNNG pretreatment. Pretreatment of Mer- cells (BE) had little effect on either cell killing or DNA crosslinking levels induced by mitozolomide or MCTIC. DNA interstrand crosslinking induced by mitozolomide and MCTIC is probably a consequence of an initial alkylation at the O6-position of guanine followed by a delayed reaction with the opposite DNA strand.
在体外实验中，发现米托唑胺及其分解产物MCTIC对BE结肠癌细胞的细胞毒性比对另一种结肠癌细胞系HT - 29细胞更强。此外，米托唑胺和MCTIC在BE细胞系中诱导了DNA链间交联，但在HT - 29细胞系中未诱导。BE细胞在修复O6 - 甲基鸟嘌呤损伤方面存在缺陷，被指定为Mer -，而HT - 29细胞在这个修复过程中功能正常，被指定为Mer +。因此，米托唑胺和MCTIC产生的DNA链间交联似乎与Mer表型相关。用DNA甲基化剂MNNG预处理HT - 29细胞（Mer +）可使米托唑胺或MCTIC产生DNA链间交联。经MNNG预处理后，HT - 29细胞对米托唑胺和MCTIC的细胞杀伤作用也变得更加敏感。对Mer -细胞（BE）进行预处理，对米托唑胺或MCTIC诱导的细胞杀伤或DNA交联水平几乎没有影响。米托唑胺和MCTIC诱导的DNA链间交联可能是鸟嘌呤O6位最初发生烷基化，随后与相对的DNA链发生延迟反应的结果。
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