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特定亚硝胺诱发局部表皮乳头瘤和癌

Induction of local epidermal papillomas and carcinoma by selected nitrosamines.

作者信息

Pour P, Wallcave L, Nagel D, Salmasi S

出版信息

Cancer Lett. 1980 Oct;10(4):365-73. doi: 10.1016/0304-3835(80)90055-5.

Abstract

Weekly cutaneous application of N-nitrosobis (2-oxopropyl)amine (BOP) at a dose of 2 mg/application to the neck area resulted in the induction of local papillomas and carcinomas in 80% of Syrian hamsters as early as 19 weeks post-treatment. In addition, a few tumors of internal organs (predominantly in the liver) were also found. N-Nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), a common metabolite of BOP and BHP, was also found to be an epidermal carcinogen at a dose of 3.8 mg/application. N-Nitrosobis(2-hydroxypropyl)amine (BHP), however, failed to induce any epidermal lesions, when applied similarly at a much higher dose level (%) mg/animal/week). In contrast to BOP and HPOP, BHP induced a high incidence of tumors in internal organs, especially pancreatic cancer, which was the only induced tumor in 5 animals. Skin absorption studies demonstrated that BHP, but not BOP is rapidly absorbed and was detectable in the blood in concentrations of up to 5.5 mug/ml as early as 15 min after carcinogen administration. The possible reasons for the differing effects of BHP and BOP upon hamster skin are discussed.

摘要

每周在叙利亚仓鼠颈部皮肤涂抹剂量为2毫克/次的N-亚硝基双(2-氧代丙基)胺(BOP),早在治疗后19周时,80%的仓鼠就诱发了局部乳头状瘤和癌。此外,还发现了一些内部器官的肿瘤(主要在肝脏)。N-亚硝基(2-羟丙基)(2-氧代丙基)胺(HPOP)是BOP和BHP的常见代谢产物,当涂抹剂量为3.8毫克/次时,也被发现是一种表皮致癌物。然而,当以高得多的剂量水平(%毫克/动物/周)进行类似涂抹时,N-亚硝基双(2-羟丙基)胺(BHP)未能诱发任何表皮病变。与BOP和HPOP相反,BHP诱发了内部器官的高发性肿瘤,尤其是胰腺癌,这是5只动物中唯一诱发的肿瘤。皮肤吸收研究表明,BHP(而非BOP)能被迅速吸收,早在给予致癌物15分钟后,血液中就能检测到其浓度高达5.5微克/毫升。文中讨论了BHP和BOP对仓鼠皮肤产生不同作用的可能原因。

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