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Tumor Promoter-dependent Mouse Leukemia Cell Line¹

Laboratory of Experimental Pathology, Aichi Cancer Center Research Institute, Tashiro-cho, Chikusa-ku, Nagoya 464 [H. K., H. H., Y. B. O., Y. N.]; National Cancer Institute, Tsukiji, Chuo-ku, Tokyo 104 [H. F., T. S.]; and Department of Pathology, Nagoya University School of Medicine, Showa-ku, Nagoya 466 [H. K., S. I.], Japan

From a spontaneous AKR/Ms thymic leukemia symbiotically cultured with thymic epithelial reticular cells, a tumor promoter-dependent cell line A65T was established by passaging the cells in medium containing 12-O-tetradecanoylphorbol-13-acetate (10 ng/ml). The in vitro growth of A65T was strictly dependent on the presence of active tumor promoters. Their action was reversible, since withdrawal of 12-O-tetradecanoylphorbol-13-acetate resulted in rapid decrease in viability of the cells. Three classes of chemically unrelated compounds sharing tumor-promoting activity in mouse skin could support the in vitro growth of A65T: plant diterpene esters; indole alkaloids; and polyacetates. Their growth effect on A65T cells quantitatively correlated well with the tumor-promoting activity in mouse skin. However, other growth stimulators of epidermal cells such as cholera toxin and epidermal growth factor failed to support the growth of A65T. It is suggested that lymphokines such as interleukin-2 and interleukin-3 were not responsible for 12-O-tetradecanoylphorbol-13-acetate-stimulated growth of A65T because concanavalin A-stimulated spleen cell-conditioned medium containing both interleukin-2 and interleukin-3 activities as well as WEHI-3 cell culture supernatant containing potent interleukin-3 activity did not stimulate the proliferation of A65T cells. Furthermore, 12-O-tetradecanoylphorbol-13-acetate did not induce production of any significant amount of either activity in A65T cells. This cell line is useful for the screening of tumor promoters in environments although, so far, all the compounds capable of stimulating A65T growth have been limited to those competing with phorbol esters for the cellular receptor. Also, the cell line provides a potential model for analyzing growth requirements of developing mouse thymic leukemias.

¹ Supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science, and Culture, Japan.

² To whom requests for reprints should be addressed.

Received 2/28/83. Accepted 7/14/83.