Autrup H, Harris C C, Schwartz R D, Trump B F, Smith L
Carcinogenesis. 1980 May;1(5):375-80. doi: 10.1093/carcin/1.5.375.
The overall metabolism of 1,2-dimethylhydrazine, and organotropic colon carcinogen in rodents, has been studied using human colon explant cultures. The binding level of 1,2-dimethylhydrazine to DNA which in this study includes both reaction of metabolites with DNA and incorporation of radioactive metabolites into DNA, showed a 100-fold variation among the 120 people studied. When different anatomical colonic sites were compared, the highest mean binding levels were found in the ascending and sigmoid colon. No significant difference in the median and mean binding levels were observed in nontumorous colon obtained surgically from patients with colon cancer and colon obtained from immediate autopsy, but decreased mean binding levels were seen in tissues obtained by surgery from patients with non-cancerous colonic disorders. Several exogenous chemicals were found to modify the metabolism. When the colon explants were co-incubated with 1,2-dimethylhydrazine and these chemicals, the binding level of 1,2-dimethylhydrazine to DNA was (a) increased by either indole 3-carbinol or phenobarbital, (b) decreased with disulfiram, butylated hydroxytoluene, or taurodeoxycholic acid, and (c) unaltered by lithocholic acid.
利用人结肠外植体培养物，对啮齿动物体内的1,2 - 二甲基肼（一种器官特异性结肠致癌物）的整体代谢进行了研究。在本研究中，1,2 - 二甲基肼与DNA的结合水平（包括代谢产物与DNA的反应以及放射性代谢产物掺入DNA）在120名研究对象中显示出100倍的差异。当比较不同的结肠解剖部位时，升结肠和乙状结肠的平均结合水平最高。从结肠癌患者手术获取的非肿瘤性结肠与尸检立即获取的结肠相比，在结合水平的中位数和平均值上未观察到显著差异，但在患有非癌性结肠疾病患者手术获取的组织中，平均结合水平降低。发现几种外源性化学物质可改变代谢。当结肠外植体与1,2 - 二甲基肼和这些化学物质共同孵育时，1,2 - 二甲基肼与DNA的结合水平：(a) 吲哚 - 3 - 甲醇或苯巴比妥可使其升高；(b) 双硫仑、丁基羟基甲苯或牛磺去氧胆酸可使其降低；(c) 石胆酸对其无影响。
