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Induction of Resistant Hepatocytes as a New Principle for a Possible Short-Term in vivo Test for Carcinogens^{1 ,2}

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

The induction of resistant hepatocytes in vivo in the rat has been observed with 21 different chemical carcinogens. The resistance was measured by the ability of the cells to proliferate as focal lesions in the presence of an environment that inhibits the original or surrounding hepatocytes from proliferation. This was created by a dietary 2-acetylaminofluorene plus a stimulus for cell proliferation, a single necrogenic dose of CCl₄. The foci were readily visualized by staining for -glutamyl transpeptidase activity. With most of the chemicals, a single administration at an appropriate time after partial hepatectomy is efficacious. However, with safrole and dieldrin, three doses over a 36-hr period were required to induce a significant number of foci of resistant hepatocytes. The presumptive preneoplastic nature of the resistant hepatocytes and the possible usefulness of this approach for the development of a new in vivo short-term test system for carcinogens are discussed.

¹ This research was supported in part by research grants from the National Cancer Institute of Canada, Medical Research Council of Canada (MA-5994), and by Contract CP-75879 and Research Grant CA-25094 from the National Cancer Institute, United States Department of Health, Education, and Welfare. A preliminary report of this research was presented at the meeting of the American Association for Cancer Research, May 1979 (31).

² Present address: First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizubo-cho, Mizuho-ku, Nagoya 467, Japan.

³ To whom requests for reprints should be addressed.

Received 10/ 1/79. Accepted 1/ 2/80.

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