Marvin C. Pankaskie

Inhibition of spermine biosynthesis and thymidine incorporation in concanavalin a transformed lymphocytes by S-adenosyl-(±)-2-methylmethionine

Summary S-Adenosyl-(±)-2-methylmethionine, an inhibitor of mammalian S-adenosyl-L-methionine decarboxylase, inhibited the increase in [ 3 H]-thymidine incorporation but did not interfere with the rise in [ 3 H]-uridine and [ 3 H]-leucine incorporation induced by concanavalin A in cultured mouse lymphocytes. Polyamine synthesis which increases during lymphocyte proliferation, was also selectively inhibited. Cellular levels of putrescine and spermidine increased despite the presence of the inhibitor but the rise in spermine concentration was blocked. Moreover, 24 hours after the addition of S-adenosyl-(±)-2-methylmethionine and concanavalian A to lymphocyte cultures, a concentration-dependent decrease in both [ 3 H]-thymidine incorporation and cellular spermine concentration was observed with dose-dependent increases in the other two polyamines. This is the first study in which selective inhibition of spermine synthesis also blocked DNA synthesis suggesting that this polyamine may participate in the regulation of proliferation in lymphocytes.