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Suppression of Saccharin-induced Mutagenicity by Interferon- in Human RSa Cells

Department of Biochemistry, School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260 [N. S.], and Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, 24-1, Hyakunincho 3 chome, Shinjuku-ku, Tokyo 169 [H. S.], Japan

Saccharin is an artificial sweetener commonly used in the formulation of foods and beverages. Sodium saccharin-induced mutagenicity is detectable in human RSa cells by estimation of cloning efficiency of ouabainresistant mutant cells and determination of K-ras codon 12 mutation in genomic DNA, analyzed by PCR and differential dot-blot hybridization. However, in this study no phenotypic or genetic mutations were detected in RSa cells cultured with human IFN (HuIFN)- before sodium saccharin treatment. The suppressive effect was lessened by transient treatment with antipain immediately after sodium saccharin treatment. Elevation of antipain-sensitive protease activity was found, furthermore, in RSa cells cultured with HuIFN- and subsequently treated with sodium saccharin. Thus, antipain-sensitive protease induction in cells tested here may be involved in suppression of the mutagenicity of saccharin by HuIFN-.

¹ To whom requests for reprints should be addressed.

Received 6/26/95. Accepted 8/24/95.