Interrelationship between tumorigenicity and the chemical nature of N-methyl-N'-aryl-N-nitrosoureas.

The tumorigenic activity of a series of N-methyl-N'-aryl-N-nitrosoureas (I-X) on mouse skin was investigated in comparison with that of N-methyl-N-nitrosourea (MNU). The tumorigenic potency of I-X was less than that of MNU, although the former are much stronger mutagens; and no correlations were found between the tumorigenicity of I-X and their mutagenicity. The major tumors induced by the methoxy and methyl derivatives, both of which have high lipophilicity, were sarcomas (fibrosarcomas and fibroanaplastic, anaplastic, and pleomorphic cell sarcomas) in contrast to the fact that squamous cell carcinomas were the major tumors induced by MNU. Although the nitrosoureas were not administered intragastrically to the animals, squamous cell carcinomas were observed in the forestomachs of mice treated with I-X, but no tumors were produced in the stomachs by MNU. Adenocarcinomas were found in the lungs of mice treated with all the nitrosoureas. Hyperplastic nodules were observed in the livers of mice treated with methoxy and hydrogen derivatives, while cysts were found with methyl derivatives.