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Protease inhibitors suppress radiation-induced malignant transformation in vitro

Abstract

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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