N-甲基甲酰胺：小鼠体内的抗肿瘤活性及代谢
N-methylformamide: antitumour activity and metabolism in mice.
作者信息
Gescher A, Gibson N W, Hickman J A, Langdon S P, Ross D, Atassi G
出版信息
Br J Cancer. 1982 Jun;45(6):843-50. doi: 10.1038/bjc.1982.136.
Abstract
The antitumour activities of N-methylformamide, N-ethylformamide and formamide against a number of murine tumours in vivo (Sarcoma 180, M5076 ovarian sarcoma and TLX5 lymphoma) have been estimated. In all cases N-methyl-formamide had significant activity, formamide had marginal or no activity and N-ethylformamide had no significant activity. N-methylformamide and N-ethylformamide were equitoxic to the TLX5 lymphoma in vitro. Formamide was found as a metabolite in the plasma and urine of animals given N-methylformamide and N-ethylformamide, but excretion profiles do not support the hypothesis that formamide is an active antitumour species formed from N-alkylformamides. No appreciable metabolism of N-methylformamide occurred under a variety of conditions with liver preparations in vitro. N-methylformamide, but not N-ethylformamide or formamide, reduced liver soluble non-protein thiols by 59.8% 1 h after administration of an effective antitumour dose.
摘要
已评估了N-甲基甲酰胺、N-乙基甲酰胺和甲酰胺对多种小鼠体内肿瘤（肉瘤180、M5076卵巢肉瘤和TLX5淋巴瘤）的抗肿瘤活性。在所有情况下，N-甲基甲酰胺具有显著活性，甲酰胺具有边缘活性或无活性，N-乙基甲酰胺无显著活性。N-甲基甲酰胺和N-乙基甲酰胺在体外对TLX5淋巴瘤具有同等毒性。在给予N-甲基甲酰胺和N-乙基甲酰胺的动物的血浆和尿液中发现甲酰胺是一种代谢产物，但排泄情况不支持甲酰胺是由N-烷基甲酰胺形成的活性抗肿瘤物质这一假设。在体外多种条件下，用肝脏制剂处理时，N-甲基甲酰胺未发生明显代谢。给予有效抗肿瘤剂量1小时后，N-甲基甲酰胺可使肝脏可溶性非蛋白硫醇减少59.8%，而N-乙基甲酰胺或甲酰胺则无此作用。
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