The effects of
periodate-oxidized adenosine, 3-deaza-adenosine and 3-deaza-(+/-)
aristeromycin, potent inhibitors of
S-adenosylhomocysteine hydrolase activity, on DNA methylation and the intracellular ratio of
S-adenosylhomocysteine and
S-adenosylmethionine have been examined in a series of murine and human tumor cell lines. A 24-h exposure of murine LC3, TA3 and B16 cells and human MeWo and K562 cells to 1-10 microM
periodate-oxidized adenosine had a very slight inhibitory effect upon DNA methylation. 3-Deaza-(+/-)
aristeromycin and 3-deaza-adenosine (50 microM) had virtually no effect upon DNA methylation in LC3 and B16 cells. In LC3 cells,
periodate-oxidized adenosine, 3-deaza-adenosine and 3-deaza-(+/-)
aristeromycin reduced the intracellular ratio of
S-adenosylmethionine/
S-adenosylhomocysteine approximately 20-, 6- and 16-fold, respectively. In murine
B16 melanoma cells,
periodate-oxidised
adenosine, 3-deaza-adenosine and 3-deaza-(+/-)
aristeromycin reduced the intracellular ratio of
S-adenosylmethionine/
S-adenosylhomocysteine approximately 17-, 13- and 32-fold, respectively. These observations indicate that the
cytosine methylation of
DNA appears to be relatively insensitive to changes in the intracellular ratio of
S-adenosylmethionine/
S-adenosylhomocysteine and that such metabolic disturbances are not likely to be the major biochemical alteration responsible for the reduced level of
DNA 5-methylcytosine found within transformed and malignant cells.