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Human T-Cell Leukemia Virus I Induction by 5-lodo-2'-deoxyuridine and N-Methyl-N'-nitro-N-nitrosoguanidine: Inhibition by Retinoids, L-Ascorbic Acid, and DL--Tocopherol¹

Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606, Japan [J. R. B., N. Y., Y. H.], and The Department of Veterinary Pathobiology, The Ohio State University, Columbus, Ohio 43210-1093 [J. R. B.]

Human T-cell leukemia virus type I was induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 5-iodo-2'-deoxyuridine (IdUrd) in the MT-1 cell line. Virus expression was monitored by immunofluorescence microscopy with GIN-14, mouse monoclonal antibodies directed toward M_r 19,000 and M_r 28,000 protein-specific virus polypeptides. MNNG (0.1 µg/ml) and IdUrd (50 µg/ml) both induced virus synthesis in MT-1 cells. MNNG-induced virus expression peaked between 24 and 48 h of incubation, whereas IdUrd induced maximum virus expression between 48 and 72 h of incubation. Superinduction resulted when MNNG was added to cells induced 48 h previously with IdUrd, but not with concomitant treatment. 13-cis-Retinoic acid, retinol, retinol aldehyde, and retinol acetate (10^-6 to 10^-9 M) were concomitantly added with IdUrd to MT-1 cells for 24, 48, and 72 h incubation. All inhibited virus induction to various degrees. The retinoids were ranked as to inhibitory activity: retinol > retinoic acid > retinol aldehyde > retinol acetate. The most sensitive period for inhibiting IdUrd induction by retinoic acid was 24 h postinduction or with concomitant treatment. Vitamin C and vitamin E inhibited IdUrd induction most effectively with 48 h incubation. Retinol and vitamin C also inhibited virus induction by MNNG. None of the retinoids, vitamin C, or vitamin E significantly inhibited virus expression in noninduced cells or were toxic to the cells at the concentrations used in these experiments.

¹ Supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, The Ministry of Health and Welfare, Japan.

² The author gratefully acknowledges the support of the Japan Society for the Promotion of Science and The Ohio State University. To whom requests for reprints should be addressed.

Received 12/ 6/84. Revised 5/ 6/85. Accepted 5/ 8/85.