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-α-Tocopherol

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.