Lijinsky W, Saavedra J E, Kovatch R M
NCI-Frederick Cancer Research Facility, BRI-Basic Research Program, MD 21701.
Chem Biol Interact. 1988;66(1-2):37-47. doi: 10.1016/0009-2797(88)90039-7.
A comparison has been made of the carcinogenic effects of nitroso-2,6-dimethylmorpholine and several hydroxylated acyclic nitrosodialkylamines derived from it or related to it in rats and Syrian hamsters. In rats nitrosodimethylmorpholine was the most potent, inducing mainly esophageal tumors. Nitrosodiethanolamine was the weakest of the five nitrosamines in both rats and hamsters. Tumors of the pancreas ducts were induced by four of the five compounds, but only in hamsters, and esophageal tumors appeared only in rats. Most of the nitrosamines induced tumors of liver and lung in both rats and hamsters. A study of alkylation of nucleic acids of the liver following treatment of rats and hamsters with the radiolabeled nitrosamines showed that nitrosodiethanolamine alkylated liver nucleic acids in rats to only a very small extent. The other four nitrosamines all gave rise to 7-methylation and O6-methylation of guanine residues in DNA of hamster liver and all but nitrosodimethylmorpholine in rat liver DNA, which corresponded quite well with the induction of liver tumors in the two species. Quantitatively, however, there was not a good correlation between liver DNA alkylation and the potency of the nitrosamine in inducing tumors.
已对亚硝基-2,6-二甲基吗啉及其衍生或相关的几种羟基化无环亚硝基二烷基胺在大鼠和叙利亚仓鼠中的致癌作用进行了比较。在大鼠中，亚硝基二甲基吗啉的致癌性最强，主要诱发食管肿瘤。亚硝基二乙醇胺在大鼠和仓鼠中都是这五种亚硝胺中致癌性最弱的。这五种化合物中的四种能诱发胰腺导管肿瘤，但仅在仓鼠中出现，而食管肿瘤仅在大鼠中出现。大多数亚硝胺在大鼠和仓鼠中都能诱发肝肿瘤和肺肿瘤。用放射性标记的亚硝胺处理大鼠和仓鼠后，对肝脏核酸烷基化的研究表明，亚硝基二乙醇胺对大鼠肝脏核酸的烷基化程度非常小。其他四种亚硝胺均能使仓鼠肝脏DNA中的鸟嘌呤残基发生7-甲基化和O6-甲基化，大鼠肝脏DNA中除亚硝基二甲基吗啉外的其他亚硝胺也能使鸟嘌呤残基发生上述甲基化，这与这两个物种中肝肿瘤的诱发情况相当吻合。然而，从数量上看，肝脏DNA烷基化与亚硝胺诱发肿瘤的能力之间并没有良好的相关性。
