LITTLE is known about the mechanisms of carcinogenesis. The fact that most carcinogens are mutagenic has led to speculation that the primary step in cancer induction may be mutational1,2; there is evidence from both in vivo2 and in vitro3 studies that a strong correlation exists between the mutagenicity and carcinogenicity of an agent. Mutagenic and carcinogenic agents, both physical and chemical, also produce similar kinds of DNA damage and repair4. Radiation-induced mutagenesis in some bacterial cells requires an error-prone DNA repair system5,6, and there is now some evidence that error-prone DNA repair may be involved in the malignant transformation of cells by radiation7,8. Protease inhibitors have been shown to suppress specifically both error-prone repair and mutagenesis in bacterial cells9,10, as well as to inhibit carcinogenesis in vivo11,12. We report here that the protease inhibitors antipain and leupeptin will suppress radiation-induced transformation in vitro as well as inhibit two-stage transformation in vitro using radiation and the promoting agent, 12-O-tetradecanoyl-phorbol-13-acetate (TPA).
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KENNEDY, A., LITTLE, J. Protease inhibitors suppress radiation-induced malignant transformation in vitro. Nature 276, 825–826 (1978). https://doi.org/10.1038/276825a0
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