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Promotion of Liver Cancer Development by Brief Exposure to Dietary 2-Acetylaminofluorene plus Partial Hepatectomy or Carbon Tetrachloride¹

Department of Pathology, University of Toronto, Toronto, Ontario M5G 1L5, Canada

Adult male Fischer rats were exposed to a necrogenic dose (200 mg/kg) of diethylnitrosamine or to nonnecrogenic doses of N-methyl-N-nitrosourea, 1,2-dimethylhydrazine, or benzo(a)pyrene following partial hepatectomy or sham hepatectomy. This treatment by itself led to no hepatocellular carcinomas by 8 to 18 months, except in animals given N-methyl-N-nitrosourea, which showed a 30% incidence by 12 months. With each treatment regimen, exposure to dietary 2-acetylaminofluorene for 2 weeks coupled with partial hepatectomy or the administration of a necrogenic dose of CCl₄, was associated with an incidence of 68 to 94% of cancer at 8, 12, or 18 months, depending upon the initiating carcinogen used. Appropriate controls showed either no hepatocellular carcinoma or a much lower incidence. It is concluded that the 2-week exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or the administration of CCl₄ has a strong promoting effect on liver carcinogenesis with four different chemical carcinogens.

¹ This research was supported by grants from the National Cancer Institute of Canada; the National Cancer Institute, NIH (CA-21157); and the Medical Research Council of Canada (MT-5594). A preliminary report of some of this research was presented at the meeting of the American Association for Cancer Research in May 1980 (1).

² Present address: Department of Pathology, Northwestern University School of Medicine, Chicago, Ill.

³ Present address: Centro de Investigationes Biomedicas, Universidad de Carabobo Maracay, Venezuela.

⁴ Present address: First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizubo-cho, Mizuho-ku, Nagoya 467, Japan.

⁵ Present address: Department of Pathology, Sapporo Medical College, S. 1, W.7 Chuo-ku, Sapporo 060, Japan.

⁶ To whom requests for reprints should be addressed.

Received 3/ 8/82. Accepted 9/ 3/82.

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