Tumorigenicity of 3'-hydroxymethyl, 3'-formyl, and 3'-carboxy derivatives of 4-(dimethylamino)azobenzene in rat liver.

Male Sprague-Dawley rats were fed a cube diet containing 2.51 mmol/kg of 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB), 3'-CH2OH-DAB, 3'-CHO-DAB, or 3'-COOH-DAB (at a level equivalent to 0.06% 3'-Me-DAB in the diet) for a period of 1 to 3 months. Almost all the livers of rats given 3'-CH2OH-DAB for a period of 2 to 3 months or 3'-Me-DAB for 3 months showed marked cirrhosis macroscopically. The common histological findings were cholangiofibrosis with or without markedly atypical bile ducts. Moreover, one hepatocellular carcinoma was found in the liver of a rat given 3'-Me-DAB and one in the liver of a rat given 3'-CH2OH-DAB for 3 months. On the other hand, 3'CHO-DAB and 3'-COOH-DAB did not induce these changes (including neoplastic nodules) at all. Consequently, 3'-CH2OH-DAB, like 3'-Me-DAB, was found to be a hepatocarcinogen.