Sava G, Zorzet S, Perissin L, Giraldi T, Lassiani L
Institute of Pharmacology, Faculty of Pharmacy, University of Trieste, Italy.
Cancer Chemother Pharmacol. 1988;21(3):241-5. doi: 10.1007/BF00262778.
To investigate the role of monomethyltriazenes as the active metabolites of antitumor dimethyltriazenes, the in vivo simultaneous treatment with an inducer (phenobarbital, PB) or an inhibitor (carbon tetrachloride, CCl4) of hepatic drug metabolism was examined in mice bearing Lewis lung carcinoma. Treatment with PB or CCl4 with the dosage and schedules employed proved to be effective in markedly modifying the N-demethylation of the three dimethyltriazenes tested, as had been determined in vitro. No unambiguous increase by PB, or decrease by CCl4, which might theoretically be expected if metabolic conversion to monomethyltriazenes was involved, was observed for the antitumor and antimetastatic activity of dimethyltriazenes. At the same time, a difference was noted between the effects on primary tumors and those on metastases. These data support the view that generalizations on the relevance of monomethyltriazenes as the active metabolites responsible for the antitumor and antimetastatic activity of dimethyltriazenes may not be valid.
为了研究单甲基三氮烯作为抗肿瘤二甲基三氮烯活性代谢产物的作用，在携带Lewis肺癌的小鼠中检测了肝药物代谢诱导剂（苯巴比妥，PB）或抑制剂（四氯化碳，CCl4）的体内同时治疗。所用剂量和方案的PB或CCl4治疗被证明可有效显著改变所测试的三种二甲基三氮烯的N-去甲基化，如体外所确定的那样。对于二甲基三氮烯的抗肿瘤和抗转移活性，未观察到PB理论上预期的明确增加或CCl4理论上预期的明确降低（如果涉及代谢转化为单甲基三氮烯的话）。同时，注意到对原发性肿瘤和转移瘤的影响存在差异。这些数据支持这样一种观点，即关于单甲基三氮烯作为负责二甲基三氮烯抗肿瘤和抗转移活性的活性代谢产物的相关性的概括可能无效。
