Inhibition off Dimethyl Sulffoxide-induced Differentiation off Friend Erythroleukemic Cells by 5'-Methylthioadenosine

5' -Methylthioadenosine is a sulfur-containing nucleoside derived from the metabolism of polyamines which is known to exert an antiproliferative effect on several cell systems in vitro, including the Friend leukemia cell system. We have investigated the role of 5'-methylthioadenosine on the dimethyl sulfoxRJe-induced differentiation of this system. At a concentration of 400 /*M, the drug strongly inhibited (80%) the induced differentiation of Friend cells, and this effect was already observable at a concentration as tow as 10 HM (36% inhibition), as evidenced by the benzidine staining procedure and by the dot-blot hybridization of globin mRNA with a human 0-globin probe. Similar results have been obtained by using 5'-S-isobutylthioadenosine, which is a synthetic structural analogue of 5' -methylthioadenosine. The block of differentiation produced by these nucleosides was not mediated by adenine (a cataboiite of both molecules) and was not reverted by spermine or spermidine, the two polyamines whose synthesis is inhibited by 5'-methylthtoadenosine. We report a decrease of the aminopropyttransferases activities (the enzymes responsible for 5'-methytthioadenosine biosynthesis) in dimethyl sulfoxide-treated Friend cells, which could lead to a decrease of the intracellular content of 5'-methylthioadenosine during the erythrokJ maturation of Friend cells. The results obtained are consistent with the hypothesis that 5'-methylthioadenosine may act as an endogenous regulator of Friend cell differentiation. © 1984, American Association for Cancer Research. All rights reserved.