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Alteration of Tumor Response in Rat Liver by Carbon Tetrachloride¹

Carcinogenesis Program, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830

From the response of Sprague-Dawley rats to (a) aminopyrine, sodium nitrite, and CCl₄; (b) aminopyrine and sodium nitrite only; or (c) dimethylnitrosamine only, it was determined that the combination of aminopyrine, sodium nitrite, and CCl₄ is highly hepatotoxic and cirrhogenous and that this combination of chemicals induces hepatocellular tumors. Of 18 animals given these 3 compounds, 6 developed hepatocellular tumors, 9 developed hemangioendothelial sarcomas (Kupffer cell sarcomas) of the liver, and all developed severe postnecrotic cirrhosis. All animals that received aminopyrine and nitrite or dimethylnitrosamine without CCl₄ developed only the vascular tumors of the liver. The absence of hepatocellular tumors after administration of dimethylnitrosamine differed from the response usually ascribed to this chemical. Gross and microscopic characteristics of hepatocellular and hemangioendothelial tumors were examined and compared.

¹ This research was jointly sponsored by the Chemical Carcinogenesis Program of the National Cancer Institute and by the U.S. Atomic Energy Commission under contract with the Union Carbide Corporation.

Received 6/10/74. Accepted 9/ 9/74.