A STUDY OF TOBACCO CARCINOGENESIS .48. CARCINOGENICITY OF N'-NITROSONORNICOTINE IN MINK (MUSTELA-VISON)
A STUDY OF TOBACCO CARCINOGENESIS .48. CARCINOGENICITY OF N'-NITROSONORNICOTINE IN MINK (MUSTELA-VISON)
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DOI：
10.1093/carcin/13.11.1957
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发表时间：
1992-11-01
期刊：
影响因子：
4.7
通讯作者：
HOFFMANN, D
中科院分区：
文献类型：
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作者：
KOPPANG, N;RIVENSON, A;HOFFMANN, D
在烟草加工和吸烟过程中，尼古丁和去甲尼古丁会产生N‘-亚硝基烟碱(NNN)，这是一种高度丰富的强致癌物质。已知NNN在小鼠、大鼠和仓鼠身上具有致癌活性。NNN致癌的主要靶器官是大鼠的食道和鼻黏膜，以及叙利亚金黄地鼠的气管和鼻黏膜。与大鼠相比，水貂(Mustela Vison)的鼻黏膜明显扩张。因此，本研究以NNN为致癌物，探讨水貂是否可以作为鼻腔癌变的非啮齿动物模型。20只随机饲养的水貂，从3周龄开始，每周接受两次SC。注射NNN，总剂量为每只动物11.9 mm，持续38周。所有处于危险中的19只水貂都在3.5年内患上了呼吸道和鼻子嗅觉区的恶性肿瘤。在大多数动物中，恶性肿瘤，主要是感觉神经上皮瘤，侵袭大脑。值得注意的是，NNN没有在水貂身上诱发其他肿瘤。在化验的3.5年中，对照动物中没有一只出现鼻部肿瘤或其他部位的肿瘤。该养殖场的历史数据没有显示任何年龄段的水貂自发发生鼻部肿瘤。这项研究支持这样的概念，即NNN是一种已被证实的多种哺乳动物的致癌物，水貂可以作为非啮齿动物、非近亲繁殖的鼻癌动物模型，特别是因为NNN只在该物种的鼻腔中诱发肿瘤，而不像在小鼠、大鼠和仓鼠中那样在其他部位诱发肿瘤。
During tobacco processing and smoking, nicotine and nornicotine give rise to N'-nitrosonornicotine (NNN), a highly abundant, strong carcinogen. NNN is known to exert carcinogenic activity in mice, rats and hamsters. Major target organs for NNN carcinogenicity in the rat are the esophagus and the nasal mucosa, and in the Syrian golden hamster trachea and nasal mucosa. In comparison with the rat, the mink (Mustela vison) has a markedly expanded nasal mucosa. Therefore, we explored in this study whether the mink could serve as a non-rodent model for nasal carcinogenesis using NNN as the carcinogen. Twenty random-bred mink, beginning at the age of 3 weeks, received twice weekly s.c. injections of NNN, a total dose of 11.9 mM per animal over a 38 week period. All of the 19 mink at risk developed malignant tumors of both the respiratory and the olfactory region of the nose within 3.5 years. In most animals the malignant tumors, primarily esthesioneuroepithelioma, invaded the brain. Remarkably, NNN induced no other tumors in the mink. None of the control animals developed nasal tumors nor tumors at other sites during the 3.5 years of the assay. The historical data from the farm did not reveal any spontaneous occurrence of nasal tumors in mink at any age. This study supports the concept that NNN is a proven carcinogen for multiple species of mammals and that the mink can serve as a non-rodent, non-inbred animal model for nasal carcinogenesis, especially since NNN induces only tumors in the nasal cavity in this species and not at other sites, as it does in mice, rats and hamsters.