Induction of rat kidney tumours by ethyl methanesulphonate and nervous tissue tumours by methyl methanesulphonate and ethyl methanesulphonate.

Abstract

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.