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N-丁基-N-(4-羟基丁基)亚硝胺及相关化合物代谢的种属差异与膀胱癌发生的关系

Species variations in the metabolism of N-butyl-N-(4-hydroxybutyl) nitrosamine and related compounds in relation to urinary bladder carcinogenesis.

作者信息

Suzuki E, Anjo T, Aoki J, Okada M

出版信息

Gan. 1983 Feb;74(1):60-8.

PMID:6840438
Abstract

Species variations in response to urinary bladder carcinogens, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN), and N,N-dibutylnitrosamine (DBN), were investigated in several animal species from the metabolic point of view. Since N-butyl-N-(3-carboxypropyl) nitrosamine (BCPN) and N-ethyl-N-(3-carboxypropyl) nitrosamine (ECPN) had been found to be the principal urinary metabolites which are responsible for the induction of bladder tumors by BBN or DBN and EHBN, respectively, in rats, acidic urinary metabolites with the N-nitroso moiety were isolated and determined by a colorimetric method after oral administration of these nitrosamines to rats, mice, hamsters, guinea pigs, and dogs. Qualitatively almost no species differences were observed among these animals in regard to the urinary metabolites except in the case of mice, in which the glycine conjugate of BCPN was isolated from the urine and identified as the principal metabolite of BBN and DBN. However, appreciable quantitative differences in the urinary excretion of BCPN or ECPN were found among these animal species, indicating that the differences in the susceptibilities of different animal species to urinary bladder carcinogenesis induced by BBN, DBN and EHBN may be closely related to the different extents of urinary excretion of the active metabolites of these nitrosamines.

摘要

从代谢角度研究了几种动物物种对膀胱致癌物N-丁基-N-(4-羟丁基)亚硝胺(BBN)、N-乙基-N-(4-羟丁基)亚硝胺(EHBN)和N,N-二丁基亚硝胺(DBN)的反应的物种差异。由于已发现N-丁基-N-(3-羧丙基)亚硝胺(BCPN)和N-乙基-N-(3-羧丙基)亚硝胺(ECPN)分别是BBN或DBN和EHBN在大鼠中诱导膀胱肿瘤的主要尿液代谢物,在给大鼠、小鼠、仓鼠、豚鼠和狗口服这些亚硝胺后,通过比色法分离并测定了带有N-亚硝基部分的酸性尿液代谢物。除了小鼠的情况外,在这些动物的尿液代谢物方面几乎没有观察到物种差异,在小鼠中,从尿液中分离出BCPN的甘氨酸共轭物并鉴定为BBN和DBN的主要代谢物。然而,在这些动物物种中发现BCPN或ECPN的尿液排泄存在明显的定量差异,这表明不同动物物种对BBN、DBN和EHBN诱导的膀胱致癌作用的易感性差异可能与这些亚硝胺活性代谢物的尿液排泄程度不同密切相关。

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