Human T-cell leukemia virus I induction by 5-iodo-2'-deoxyuridine and N-methyl-N'-nitro-N-nitrosoguanidine: inhibition by retinoids, L-ascorbic acid, and DL-alpha-tocopherol.
Human T-cell leukemia virus type I was induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 5-iodo-2'-deoxyuridine (ldUrd) in the MT-1 cell line. Virus expression was monitored by immunofluorescence microscopy with GIN-14, mouse monoclonal antibodies directed toward Mr 19,000 and Mr 28,000 protein-specific virus polypeptides. MNNG (0.1 micrograms/ml) and ldUrd (50 micrograms/ml) both induced virus synthesis in MT-1 cells. MNNG-induced virus expression peaked between 24 and 48 h of incubation, whereas ldUrd induced maximum virus expression between 48 and 72 h of incubation. Superinduction resulted when MNNG was added to cells induced 48 h previously with ldUrd, 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 ldUrd 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 greater than retinoic acid greater than retinol aldehyde greater than retinol acetate. The most sensitive period for inhibiting ldUrd induction by retinoic acid was 24 h postinduction or with concomitant treatment. Vitamin C and vitamin E inhibited ldUrd 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.
Blakeslee
J R
JR
Yamamoto
N
N
Hinuma
Y
Y
D000956:Antigens, Viral / Q000096:biosynthesis; D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D017977:Deltaretrovirus / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007065:Idoxuridine / Q000494:pharmacology*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D012176:Retinoids / Q000494:pharmacology*; D013997:Time Factors; D014775:Virus Activation / Q000187:drug effects*; D014810:Vitamin E / Q000494:pharmacology*
D000956:Antigens, Viral; D012176:Retinoids; D008769:Methylnitronitrosoguanidine; D014810:Vitamin E; D007065:Idoxuridine; D001205:Ascorbic Acid