Kato S, Yamashita K, Kim T, Tajiri T, Onda M, Sato S
Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan.
Mutat Res. 1988 Nov;202(1):85-91. doi: 10.1016/0027-5107(88)90167-4.
DNA adducts of mitomycin C (MMC) were detected by 32P-postlabeling analysis in both surgical specimens and an autopsy sample of the liver of patients with hepatocellular carcinoma who had received chemotherapy with MMC. Four kinds of adducts were detected in all 6 patients treated with MMC. These adducts had identical chromatographic mobilities to those of adducts in the liver of rats treated with MMC, but 1 additional adduct was detected in rat liver. In patients treated with MMC, about 3 adducts/10(8) nucleotides were found 4 days after MMC treatment, and 1 adduct/10(8) nucleotides 14 days after treatment and the latter level was maintained for up to 56 days. MMC-DNA adducts were also detected in peripheral blood leukocytes from a patient 1 and 7 days after MMC treatment, at levels of 1 and 0.6 adduct/10(8) nucleotides, respectively. These results suggest the tumor-initiating activity of MMC in humans.
通过³²P后标记分析法在接受丝裂霉素C(MMC)化疗的肝细胞癌患者的手术标本和肝脏尸检样本中检测到MMC的DNA加合物。在所有6例接受MMC治疗的患者中均检测到4种加合物。这些加合物的色谱迁移率与用MMC处理的大鼠肝脏中的加合物相同,但在大鼠肝脏中还检测到1种额外的加合物。在用MMC治疗的患者中,MMC治疗后4天发现约3个加合物/10⁸个核苷酸,治疗后14天为1个加合物/10⁸个核苷酸,且后者水平维持长达56天。在1例患者接受MMC治疗后1天和7天的外周血白细胞中也检测到MMC-DNA加合物,水平分别为1个加合物/10⁸个核苷酸和0.6个加合物/10⁸个核苷酸。这些结果提示MMC在人类中的肿瘤起始活性。