Suzuki E, Takeda Y, Mochizuki M, Hashimoto Y, Okada M
Gan. 1981 Aug;72(4):539-46.
The metabolic fate and carcinogenicity fo three omega-hydroxy derivatives of N-alkyl-N-(4-hydroxybutyl) nitrosamines, potent bladder carcinogens, were investigated in the rat. They were N-(2-hydroxyethyl)-N-(4-hydroxybutyl)-nitrosamine (HEHBN), N-(3-hydroxypropyl)-N-(4-hydroxybutyl) nitrosamine (HPHBN), and N-N-bis(4-hydroxybutyl) nitrosamine (BHBN). The principal urinary metabolite of HEHBN as well as HPHBN was identified as the corresponding 3-carboxypropyl compound, while the main metabolite of BHBN was N,N-bis (3-carboxypropyl) nitrosamine, indicating the preferential metabolic oxidation of the 4-hydroxybutyl chain to the 3-carboxypropyl group in the N-(omega-hydroxyalkyl)-N-(4-hydroxybutyl) nitrosamines. All three N-nitrosamines having the 4-hydroxybutyl chain induced neither bladder tumor nor any tumor in other organs under conditions similar to those used for N-alkyl-N-(4-hydroxy-butyl) nitrosamines. The essential structural and metabolic requirements in N-nitrosamines for the induction of bladder cancer in the rat are discussed.
对三种N-烷基-N-(4-羟丁基)亚硝胺的ω-羟基衍生物（强效膀胱致癌物）在大鼠体内的代谢归宿和致癌性进行了研究。它们分别是N-(2-羟乙基)-N-(4-羟丁基)亚硝胺（HEHBN）、N-(3-羟丙基)-N-(4-羟丁基)亚硝胺（HPHBN）和N,N-双(4-羟丁基)亚硝胺（BHBN）。HEHBN以及HPHBN的主要尿液代谢产物被鉴定为相应的3-羧丙基化合物，而BHBN的主要代谢产物是N,N-双(3-羧丙基)亚硝胺，这表明在N-(ω-羟烷基)-N-(4-羟丁基)亚硝胺中，4-羟丁基链优先代谢氧化为3-羧丙基基团。在与用于N-烷基-N-(4-羟丁基)亚硝胺相似的条件下，所有具有4-羟丁基链的三种N-亚硝胺均未诱发膀胱肿瘤或其他器官的任何肿瘤。文中讨论了N-亚硝胺在大鼠体内诱发膀胱癌的基本结构和代谢要求。
