Lijinsky W, Saavedra J E, Kovatch R M
Laboratory of Chemical and Physical Carcinogenesis, NCI-Frederick Cancer Research and Development Center, MD 21702.
In Vivo. 1991 Mar-Apr;5(2):85-9.
A number of nitrosamines that have been studied by administration to rats as solutions in drinking water have been examined by gavage administration of similar doses, for assessment of the role of pharmacokinetics in organ-specific carcinogenesis. Methylnitrosoethylamine was more effective as a liver carcinogen by gavage than in drinking water and gave rise to tumors of the lung and nasal mucosa by the former route, but not the latter. By gavage, methylnitroso-2-oxopropylamine and methylnitroso-2-hydroxypropylamine induced mainly tumors of the esophagus, as they did when given to rats in drinking water, but the potency was greater by gavage. At a higher dose rate (85 micromoles per week) methylnitrosohydroxypropylamine induced a high incidence of mesenchymal tumors of the kidney and lung tumors, in addition to esophageal tumors, but methylnitrosooxopropylamine did not. The tobacco-specific carcinogen NNK induced tumors of the liver, and to a lesser extent, of the lung and nasal mucosa when given by gavage to rats, as it did by other routes of administration. The similarly basic nitrosamine methylnitroso-N, N-dimethylaminoethylamine was equally potent, whether administered by gavage or in drinking water to rats, and gave rise only to tumors of the esophagus. The cyclic nitrosamine nitrosomorpholine was equally effective by gavage and in drinking water, but induced in rats more esophageal tumors by gavage in addition to a high incidence of liver tumors. Its 2-hydroxy derivative, a postulated metabolic intermediate of nitrosodiethanolamine, was a very much weaker carcinogen than either the latter or nitrosomorpholine, and induced low incidences of liver and lung tumors toward the end of the lifespan of the rats.
通过将一些亚硝胺以饮水溶液的形式给予大鼠进行研究后，又通过灌胃给予类似剂量来进行检测，以评估药代动力学在器官特异性致癌作用中的作用。甲基亚硝基乙胺通过灌胃作为肝脏致癌物比通过饮水更有效，并且通过前一种途径会引发肺部和鼻黏膜肿瘤，而通过饮水则不会。通过灌胃，甲基亚硝基 - 2 - 氧代丙胺和甲基亚硝基 - 2 - 羟丙胺主要诱发食管肿瘤，与给予大鼠饮水时的情况相同，但灌胃时的致癌效力更强。在较高剂量率（每周85微摩尔）下，甲基亚硝基羟丙胺除了诱发食管肿瘤外，还诱发了高发生率的肾脏间叶性肿瘤和肺部肿瘤，但甲基亚硝基氧代丙胺则没有。烟草特异性致癌物NNK通过灌胃给予大鼠时会诱发肝脏肿瘤，在较小程度上还会诱发肺部和鼻黏膜肿瘤，其他给药途径也是如此。同样呈碱性的亚硝胺甲基亚硝基 - N，N - 二甲基氨基乙胺，无论通过灌胃还是饮水给予大鼠，其致癌效力相同，并且仅诱发食管肿瘤。环状亚硝胺亚硝基吗啉通过灌胃和饮水的效果相同，但通过灌胃给予大鼠时，除了高发生率的肝脏肿瘤外，还诱发了更多的食管肿瘤。其2 - 羟基衍生物，被认为是亚硝基二乙醇胺的代谢中间产物，是一种比后者或亚硝基吗啉弱得多的致癌物，在大鼠寿命接近尾声时诱发肝脏和肺部肿瘤的发生率较低。
