STIMULATION OF DNA-SYNTHESIS IN UNTRANSFORMED CELLS BY THE ANTIVIRAL AND ANTITUMORAL COMPOUND TRICYCLODECAN-9-YL-XANTHOGENATE (D609)

The antiviral and antitumor xanthate compound tricyclodecan-9-yl-xanth ogenate (D609) is best known for its inhibitory effect on phosphatidyl choline-specific phospholipase C activity. Now we report that in NIH 3 T3 cells, but not in several transformed cell types tested, D609 stimu lated DNA synthesis when phosphocholine (PCho), insulin, or ATP was al so present. Maximal co-mitogenic effects of D609 were observed at 5 mu g/mL, a concentration 4-6 times lower than that required to inhibit p hospholipase C activity. The synergistic mitogenic effects of D609 and PCho, but not of D609 and insulin, were associated with activation of p42 and, to a lesser extent, p44 mitogen-activated protein (MAP) kina ses. The results raise the possibility that the mitogenic activity of D609 in untransformed cells may contribute to its antiviral and antitu mor effects. (C) 1998 Elsevier Science Inc.