Studies on the Carcinogenic Activity of Protein-Denaturing Agents: Hepatocarcinogenicity of Dioxane2

Abstract

The carcinogenic activity of diethylformamide, diethylacetamide, N,N′-dimethyl-N,N′-dinitrosophthalamide, heptylamine, and dioxane, compounds selected both because of their potency to denature proteins and their structural resemblance to nitrosamine derivatives, was investigated. Dioxane, when administered orally, was found to be a hepatic carcinogen, producing hepatomas in 6 of 26 rats. Diethylacetamide ingestion produced a transitional cell carcinoma of the kidney in 1 of 30 rats. Dioxane, diethylacetamide, and N,N′-dimethyl-N,N′-dinitrosoph-thalamide caused severe kidney damage. The possible relationship between the carcinogenic activity of dioxane and its capacity to alter cellular metabolic control sites by virtue of its protein-denaturing ability is discussed.