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Tumor Copromoting Activity of -Interferon in the Murine Skin Multistage Carcinogenesis Model¹

The University of Texas M. D. Anderson Cancer Center, Science Park—Research Division, Smithville, Texas 78957

Recombinant DNA-derived murine -interferon (rMuIFN-) was tested in the murine skin multistage carcinogenesis model as a modulator of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. Female SENCAR mice were topically initiated with 7,12-dimethylbenz(a)anthracene and promoted twice weekly with TPA for 20 weeks. Intraperitoneal administration of rMuIFN- 1 day prior to TPA treatment affected neither the kinetics of papilloma development nor the percentage of mice that developed tumors. However, papilloma multiplicities could be either inhibited or increased depending upon the dose of rMuIFN-. Papilloma multiplicities for mice receiving 100, 500, 1000, and 5000 units of rMuIFN- were 184, 122, 105, and 84% of TPA control values, respectively. In contrast, twice weekly i.p. treatments of 7,12-dimethylbenz(a)anthracene initiated mice with only rMuIFN- for 20 weeks did not promote the development of any tumors. Consequently, TPA functioned as a copromoter in those situations in which combined TPA and IFN- treatments elevated papilloma multiplicities. Collectively, the current study demonstrates that rMuIFN- can systemically modulate TPA-dependent promotion in mouse skin.

¹ This project was supported by National Cancer Institute Grants CA-40823 and CA-34469 (DHHS) and American Cancer Society Grant IFN-16.

² To whom requests for reprints should be addressed.

Received 8/15/88. Revised 11/28/88. Accepted 12/ 2/88.

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