Fiala E S
Cancer. 1977 Nov;40(5 Suppl):2436-45. doi: 10.1002/1097-0142(197711)40:5+<2436::aid-cncr2820400908>3.0.co;2-u.
Colon cancer can be induced reliably in rodents with 1,2-dimethylhydrazine and azoxymethane (AOM). Our studies deal with the mode of action of these compounds and their organotropism. A partial summary of our previous work on the metabolism of 1,2-dimethylhydrazine and its inhibition by disulfiram, carbon disulfide and other thiono-sulfur compounds is presented. On-going studies with AOM-14C indicate that in male F-344 rats, this carcinogen is rapidly metabolized to 14CO2 (37%, 48 hours), and to methylazoxymethanol-14C (MAM) (0.6--1%), which, along with other metabolites, appears in the urine. Pretreatment of rats with phenobarbital or chyrsene increased exhaled 14CO2 to 53% and 65%, respectively. Pretreatment with disulfiram or CS2 causes a complete, although transient, inhibition of exhaled 14CO2, decreases urinary MAM, and increases significantly the levels of unmetabolized AOM in the exhaled air and in urine. Thus, phenobarbital and chrysene appear to stimulate, while disulfiram and CS2 appear to inhibit, the metabolism of AOM. In vitro hydroxylation of AOM to MAM was demonstrated with rat liver homogenates and microsomal fractions. A hypothetical scheme for the endogenous formation of AOM is presented.
用1,2 - 二甲基肼和偶氮甲烷（AOM）可在啮齿动物中可靠地诱发结肠癌。我们的研究涉及这些化合物的作用方式及其器官嗜性。本文介绍了我们先前关于1,2 - 二甲基肼代谢及其被双硫仑、二硫化碳和其他硫代硫化合物抑制的工作的部分总结。对AOM - 14C的正在进行的研究表明，在雄性F - 344大鼠中，这种致癌物迅速代谢为14CO2（37%，48小时），以及甲基偶氮甲醇 - 14C（MAM）（0.6 - 1%），MAM与其他代谢物一起出现在尿液中。用苯巴比妥或芘预处理大鼠分别使呼出的14CO2增加到53%和65%。用双硫仑或二硫化碳预处理会导致呼出的14CO2完全但短暂地受到抑制，减少尿中MAM，并显著增加呼出气体和尿液中未代谢AOM的水平。因此，苯巴比妥和芘似乎刺激AOM的代谢，而双硫仑和二硫化碳似乎抑制AOM的代谢。用大鼠肝脏匀浆和微粒体部分证明了AOM在体外羟基化为MAM。本文提出了AOM内源性形成的假设方案。
