Büch T R, Zeller W J
German Cancer Research Center Heidelberg (DKFZ).
Anticancer Res. 2002 Mar-Apr;22(2A):697-701.
BCNU was reported to have about a 6- to 8- fold lower cytotoxic potency than ACNU in cell lines naturally deficient in O6-AGT. In seven tumor cell lines with an O6-AGT activity ranging from 40 to 360 fmol/mg the cytotoxic potency of BCNU, ACNU and HeCNU, without and after O6-AGT depletion by O6-BG, was determined. Without O6-AGT depletion, BCNU was superior to both other drugs in tumor cells with high O6-AGT activity. After O6-AGT depletion, the cytotoxic potency (comparison of IC50 values) of ACNU was higher than that of BCNU (p=0.016) or that of HeCNU (p=0.016) in all tumor cell lines. We conclude that (without O6-AGT depletion) BCNU is the drug of choice especially in tumor cells with high transferase activity. The higher cytotoxic potency of ACNU after O6-AGT depletion as compared to BCNU after O6-AGT depletion is countered by the higher toxicity of ACNU in patients necessitating a clinical dose reduction as compared to BCNU. Thus, we would not expect superiority of ACNU + O6-BG over BCNU+ O6-BG after systemic administration.
据报道，在天然缺乏O6-烷基鸟嘌呤-DNA烷基转移酶（O6-AGT）的细胞系中，卡莫司汀（BCNU）的细胞毒性效力比阿糖胞苷氮芥（ACNU）低约6至8倍。在7种O6-AGT活性范围为40至360 fmol/mg的肿瘤细胞系中，测定了BCNU、ACNU和环己亚硝脲（HeCNU）在未用O6-苄基鸟嘌呤（O6-BG）耗尽O6-AGT以及耗尽后的细胞毒性效力。在未耗尽O6-AGT时，BCNU在具有高O6-AGT活性的肿瘤细胞中优于其他两种药物。在耗尽O6-AGT后，在所有肿瘤细胞系中，ACNU的细胞毒性效力（IC50值比较）高于BCNU（p = 0.016）或HeCNU（p = 0.016）。我们得出结论，（在未耗尽O6-AGT的情况下）BCNU是首选药物，尤其是在具有高转移酶活性的肿瘤细胞中。与BCNU相比，ACNU在耗尽O6-AGT后的细胞毒性效力更高，但ACNU在患者中的毒性更高，这使得其临床剂量需要比BCNU降低。因此，我们预计全身给药后，ACNU + O6-BG不会优于BCNU + O6-BG。
