Hoffman D, Rivenson A, Adams J D, Juchatz A, Vinchkoski N, Hecht S S
Cancer Res. 1983 Jun;43(6):2521-4.
N-Nitrosodiethanolamine was assayed for carcinogenicity in Syrian golden hamsters by s.c. injection, topical application, and oral cavity swabbing. Three groups of 30 hamsters each received 27 weekly s.c. injections of either 500, 170, or 58 mg of N-nitrosodiethanolamine per kg in 0.9% NaCl solution. In the group treated with 500 mg/kg, 19 of 30 animals developed nasal cavity tumors, 7 of 30 had tracheal tumors, and 2 of 30 had tumors of the larynx. Among the animals treated with 170 mg/kg, 7 of 29 presented with nasal cavity tumors and 4 of 29 presented with tracheal tumors. In the group treated with 58 mg/kg, only two tracheal tumors were observed. Acetone solutions of N-nitrosodiethanolamine were applied to the shaved backs of three groups of 30 hamsters, each three times weekly for 36 weeks, at doses of 25, 8, or 2.5 mg; the total doses were the same as in the groups treated by s.c. injection. At the 25-mg dose level, 5 of 30 animals developed nasal cavity tumors and 4 of 30 animals had tumors of the trachea. No skin tumors were observed. The incidence of respiratory tract tumors in the groups treated with 8 or 2.5 mg was not significant compared to controls. The oral cavities of 40 hamsters were swabbed three times weekly for 45 weeks with 20 mg of N-nitrosodiethanolamine; the total dose was the same as the highest doses given by s.c. or topical administration. Seventeen of 38 hamsters had nasal cavity tumors, 6 of 38 developed tracheal tumors, and 1 of 38 presented with a tumor of the larynx. No tumors were observed in the oral cavity. The results of this study demonstrate that N-nitrosodiethanolamine is organospecific for the Syrian golden hamster nasal cavity and trachea and that it induces tumors in these sites at doses lower than previously reported.
通过皮下注射、局部涂抹和口腔擦拭的方式,对叙利亚金黄地鼠进行了N-亚硝基二乙醇胺的致癌性检测。三组,每组30只仓鼠,每周皮下注射27次,剂量分别为每千克500、170或58毫克的N-亚硝基二乙醇胺,溶于0.9%的氯化钠溶液中。在接受500毫克/千克剂量治疗的组中,30只动物中有19只出现鼻腔肿瘤,30只中有7只出现气管肿瘤,30只中有2只出现喉部肿瘤。在接受170毫克/千克治疗的动物中,29只中有7只出现鼻腔肿瘤,29只中有4只出现气管肿瘤。在接受58毫克/千克治疗的组中,仅观察到两例气管肿瘤。将N-亚硝基二乙醇胺的丙酮溶液涂抹于三组,每组30只仓鼠剃毛后的背部,每周三次,共36周,剂量分别为25、8或2.5毫克;总剂量与皮下注射组相同。在25毫克剂量水平下,30只动物中有5只出现鼻腔肿瘤,30只动物中有4只出现气管肿瘤。未观察到皮肤肿瘤。与对照组相比,接受8或2.5毫克治疗的组中呼吸道肿瘤的发生率无显著差异。40只仓鼠的口腔每周擦拭三次,持续45周,使用20毫克的N-亚硝基二乙醇胺;总剂量与皮下注射或局部给药的最高剂量相同。38只仓鼠中有17只出现鼻腔肿瘤,38只中有6只出现气管肿瘤,38只中有1只出现喉部肿瘤。口腔未观察到肿瘤。本研究结果表明,N-亚硝基二乙醇胺对叙利亚金黄地鼠的鼻腔和气管具有器官特异性,并且在低于先前报道的剂量下即可在这些部位诱发肿瘤。