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Promotion by Dietary Phenobarbital of Hepatocarcinogenesis by 2-Methyl-N,N-dimethyl-4-aminoazobenzene in the Rat¹

Department of Pathology, Cancer Institute, Tokyo 170, Japan [T. K.], and McArdle Laboratory for Cancer Research, The Medical School, University of Wisconsin, Madison, Wisconsin 53706 [H. C. P., E. C. M., J. A. M.]

The hepatocarcinogenicity of 2-methyl-N,N-dimethyl-4-aminoazobenzene, previously shown to be noncarcinogenic in adult rats in the absence of further treatment, was observed by following a 1- to 6-week period of feeding this dye to weanling rats with the dietary administration of 0.05% phenobarbital for up to 70 weeks. Many large hepatocellular carcinomas developed in the phenobarbital-treated animals by 72 weeks, whereas a very small number of tiny neoplastic nodules, including one carcinoma, were seen in the rats not given this drug. This study suggests that the use of promoting agents, following the short-term administration of weak carcinogens for the liver, can be useful in demonstrating the initiating activity of such compounds. This system may be useful in the identification of such agents in the environment.

¹ This research was supported in part by Grant CA-07175 from the National Cancer Institute.

Received 5/17/78. Accepted 10/ 3/78.