Hecht S S, Rivenson A, Braley J, DiBello J, Adams J D, Hoffmann D
Cancer Res. 1986 Aug;46(8):4162-6.
The tumorigenic activities toward the oral cavity of snuff, its extracts, and two of its major nitrosamines, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were evaluated in male F344 rats. In one protocol, groups of 21-30 rats were treated beginning at age 10 weeks by chronic application to the oral cavity for 131 weeks of either H2O, an H2O extract of snuff, an H2O extract of snuff enriched with ten times its indigenous concentration of NNN and NNK, or with NNN and NNK in H2O. The incidence of oral cavity tumors in the rats treated with NNN and NNK was 8 of 30, compared to 0 of 30 in controls (P less than 0.05). These results demonstrate that NNN and NNK can induce tumors locally in the oral cavity of F344 rats. Oral cavity tumors were also observed in 3 of 30 rats treated with snuff extract enriched with NNN and NNK, but not in the rats treated with snuff extract alone. In a second protocol, a test canal was surgically created in the lower lip of groups of 21-32 rats, and either snuff, H2O-extracted snuff, or snuff enriched with its own H2O extract was inserted in the test canal 5 times weekly for 116 weeks. A group of 10 control rats had surgery only. Among the 32 rats treated with snuff, 3 had oral cavity tumors; one was a squamous cell carcinoma originating in the test canal and invading the gingiva, one was a papilloma of the test canal, and one was a papilloma of the hard palate. Oral cavity tumors were also observed in 2 of 21 rats treated with H2O-extracted snuff and 1 of 32 rats treated with snuff enriched with its H2O extract. Oral tumors were not observed in control rats. The results of this study indicate that snuff and individual nitrosamines present in snuff can induce oral cavity tumors in F344 rats and support the epidemiological observations which indicate that snuff dipping causes oral cancer in man.
在雄性F344大鼠中评估了鼻烟及其提取物以及两种主要亚硝胺——N'-亚硝基降烟碱（NNN）和4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）对口腔的致瘤活性。在一个实验方案中，每组21 - 30只大鼠从10周龄开始，通过向口腔慢性给药131周，给药物质分别为水、鼻烟的水提取物、富含其自身NNN和NNK浓度10倍的鼻烟水提取物，或NNN和NNK的水溶液。用NNN和NNK处理的大鼠中口腔肿瘤的发生率为30只中有8只，而对照组30只中为0只（P小于0.05）。这些结果表明，NNN和NNK可在F344大鼠口腔中局部诱导肿瘤。在30只接受富含NNN和NNK的鼻烟提取物处理的大鼠中也观察到3只出现口腔肿瘤，但在仅接受鼻烟提取物处理的大鼠中未观察到。在第二个实验方案中，在每组21 - 32只大鼠的下唇手术创建一个测试通道，每周5次将鼻烟、水提取的鼻烟或富含其水提取物的鼻烟插入测试通道，持续116周。一组10只对照大鼠仅进行手术。在32只接受鼻烟处理的大鼠中，3只出现口腔肿瘤；一只为起源于测试通道并侵犯牙龈的鳞状细胞癌，一只为测试通道的乳头状瘤，一只为硬腭的乳头状瘤。在21只接受水提取鼻烟处理的大鼠中有2只以及32只接受富含其水提取物鼻烟处理的大鼠中有1只也观察到口腔肿瘤。对照大鼠中未观察到口腔肿瘤。本研究结果表明，鼻烟以及鼻烟中存在的个别亚硝胺可在F344大鼠中诱导口腔肿瘤，并支持了表明嚼鼻烟会导致人类口腔癌的流行病学观察结果。
