Carcinogenicity of methylated nitrosopiperidines

The carcinogenicity of nitrosopiperidine and five methylated derivatives was compared by feeding them to rats at equimolar concentrations in drinking water, at the rate of 20 ml per day, 5 days a week. The maximum treatment time was 50 weeks. Nitrosopiperidine, 2-methyl-, 3-methyl- and 4-methyl-nitrosopiperidine induced tumors of the nasal turbinates or upper gastrointestinal tract in almost 100% of the animals. There was a significantly longer time to death from these tumors in the group treated with 2-methylnitrosopiperidine and a number of hepatocellular carcinomas appeared in this longer lived group. Very few tumors of these sites were seen in rats treated with 2,6-dimethyl- or 2,2,6,6-tetramethyl-nitrosopiperidine. It was concluded that blockage by methyl groups of one or more carbon atoms alpha to the nitroso function in nitrosopiperidine significantly reduces carcinogenic activity of the molecule.