Lijinsky W
IARC Sci Publ. 1982(41):533-42.
The effects of changes on chemical structure among groups of closely related nitrosamines on their carcinogenic effectiveness, including both potency and target organ specificity, have been examined by chronic oral administration of the nitrosamines to rats. The effects of deuterium substitution for hydrogen at various positions supports the concept that oxidation at the alpha position to the nitroso function is usually a key step in activation of carcinogenic nitrosamines. Methyl substituents at the alpha position reduce carcinogenic potency, supporting the same idea. A large number of derivatives of nitrosopiperidine have shown a large variation in carcinogenicity, not simply explained by differences in the relative rates of alpha oxidation. The effects of methyl substitution on the carcinogenicity of nitrosomorpholine and nitrosooxazolidine were opposite, although the unsubstituted compounds were of almost identical carcinogenic activity. The variations in the response of rats to a large series of nitrosodialkylamines indicated that they might be metabolized similarly, giving one or more common products which are the proximate carcinogens, and these biological effects can be related to the results of studies of the metabolism of these compounds in rats.
通过对大鼠长期口服亚硝胺，研究了密切相关的亚硝胺组之间化学结构变化对其致癌效力（包括致癌强度和靶器官特异性）的影响。在不同位置用氘取代氢的影响支持了这样一种概念，即亚硝基官能团α位的氧化通常是致癌亚硝胺活化的关键步骤。α位的甲基取代基降低了致癌强度，支持了相同的观点。大量亚硝基哌啶衍生物显示出致癌性有很大差异，不能简单地用α氧化相对速率的差异来解释。甲基取代对亚硝基吗啉和亚硝基恶唑烷致癌性的影响相反，尽管未取代的化合物具有几乎相同的致癌活性。大鼠对一系列亚硝二烷基胺反应的变化表明，它们可能以相似的方式代谢，产生一种或多种作为直接致癌物的共同产物，这些生物学效应可能与这些化合物在大鼠体内的代谢研究结果相关。
