Correlation between growth inhibition and presence of 5'-methylthioadenosine in cells treated with interferon

Treatment with interferon of several lines of human and murine cells resulted in a modest increase of the S- adenyosylmethionine level and in a greater increase of the S-adenosylhomocysteine level, with a consequent decrease in the S- adenyosylmethionine /S-adenosylhomocysteine ratio. These results confirmed a previous report (F. de Ferra and C. Baglioni , J. Biol. Chem., 258: 2118-2121, 1983) of such an effect of interferon on HeLa cells. The increase in S- adenyosylmethionine and S-adenosylhomocysteine was not observed in lymphoblastoid Raji cells, which are not growth inhibited by interferon. When Daudi cells and two other cell lines sensitive to growth inhibition by interferon were labeled with [35S]methionine, two novel labeled compounds were detected by high-pressure liquid chromatography analysis of cell extracts. These compounds were not present in untreated cells, and were either absent or present in reduced amount in extracts of cells resistant to the antiproliferative effect of interferon. One of the labeled compounds was tentatively identified with 5'-methylthioadenosine (MTA), a naturally occurring nucleoside, which was previously shown to inhibit murine lymphoid cell proliferation. Addition of MTA to cultures of different cell lines resulted in inhibition of cell growth. When the MTA concentration was measured in Daudi cells treated in this way, a relatively low concentration of MTA was detected, which was comparable to that found in interferon-treated cells. It seems possible that the presence of MTA in interferon-treated cells contributes to the inhibition of cell growth.