Induction of Rat Kidney Tumours by Ethyl Methanesulphonate and Nervous Tissue Tumours by Methyl Methanesulphonate and Ethyl Methanesulphonate
Induction of Rat Kidney Tumours by Ethyl Methanesulphonate and Nervous Tissue Tumours by Methyl Methanesulphonate and Ethyl Methanesulphonate
复制标题
甲磺酸乙酯诱导大鼠肾肿瘤和甲磺酸甲酯和甲磺酸乙酯诱导大鼠神经组织肿瘤
作者：
P. Swann;P. Magee
N-亚硝基化合物包括大量非常有效和通用的致癌物。施用这些化合物中最简单的二甲基亚硝胺，导致核酸和蛋白质的甲基化，并且在最终出现肿瘤的器官中达到最高水平的甲基化。核酸的烷基化已经被发现与其他致癌的亚硝基化合物，但烷基化的意义，这些化合物的致癌活性仍然是未知的，和任何假设的一个批评，表明细胞成分的烷基化和致癌作用之间的联系一直是，大多数已知的烷化剂的致癌活性低3，在致癌活性与一些亚硝基化合物相比。举例来说，没有一种烷化剂的致癌能力可与N-甲基-N-亚硝基脲相比，后者在单次服用后会诱发肠道、肾脏和大脑肿瘤4。几个研究小组报告称，某些烷化剂会增加小鼠肺腺瘤的发病率，亚历山大和Connell 5的一份有趣报告称，甲磺酸乙酯也会诱导小鼠肾肿瘤。不幸的是，他们的工作没有包括组织学数据，其中一位作者认为肿瘤可能是肺部肿瘤的转移。在这里，我们报告说，简单的烷化剂甲磺酸乙酯将诱导原发性肾脏肿瘤的发病率很高，在组织学外观上与二甲基亚硝胺和N-甲基-N-亚硝基脲诱导的肿瘤没有区别，也报告了一个小的，但显着数量的神经系统肿瘤发生在大鼠治疗甲磺酸甲酯和甲磺酸乙酯。
THE N-nitroso compounds include a large number of very potent and versatile carcinogens. Administration of the most simple of these compounds, dimethylnitrosamine, results in methylation of nucleic acids and proteins1 and the highest levels of methylation were achieved in those organs in which tumours eventually appeared2. Alkylation of nucleic acids has since been found with other carcinogenic nitroso compounds, but the significance of alkylation in the carcinogenic activity of these compounds is still unknown, and one criticism of any hypothesis suggesting a connexion between alkylation of cellular constituents and carcinogenesis has been that the carcinogenic activity of most known alkylating agents is low3, and none compare in carcinogenic activity with some nitroso compounds. For example, no alkylating agent has carcinogenic potency comparable with that of N-methyl-N-nitrosourea, which will induce tumours of the intestinal tract, the kidney and the brain after a single dose4. Several groups have reported that some alkylating agents will increase the incidence of lung adenomas in mice, and there has been an interesting report by Alexander and Connell5 that ethyl methanesulphonate will also induce kidney tumours in mice. Unfortunately their work did not include histological data and one of the authors suggested that the tumours might have been metastases from the tumours in the lungs. Here we report that the simple alkylating agent ethyl methanesulphonate will induce a high incidence of primary kidney tumours, indistinguishable in histological appearance from those induced by dimethylnitrosamines and N-methyl-N-nitrosourea, and also report a small but significant number of tumours of the nervous system occurring in rats treated with methyl methanesulphonate and ethyl methanesulphonate.