APOPTOSIS INDUCED BY MODIFIED RIBONUCLEOSIDES IN HUMAN CELL-CULTURE SYSTEMS

The in vitro modulation of apoptosis and cell proliferation by modifie d in comparison with non-modified ribonucleosides was investigated for the first time using peripheral blood lymphocytes, HL-60 cells and Ca co-2 cells as human cell culture models. Modulating effects of several ribonucleosides were found in the range of 10(-7)-10(-3) mol/l. The f ollowing ribonucleosides induced significant apoptosis of HL-60 cells: adenosine, N-6-dimethyladenosine, N-6-(2-isopentenyl)-adenosine, N-2- dimethylguanosine. A significant apoptotic effect on PBL was found wit h N-6-dimethyladenosine and N-6-(2-isopentenyl)-adenosine. N-6-Dimethy ladenosine, N-6-(2-isopentenyl)-adenosine and guanosine had a pronounc ed inhibitory effect on Caco-2 cell apoptosis, Regarding the known fun ction of ribonucleosides as pathobiochemical marker molecules for canc er, the possibility of a selective apoptotic effect against malignant cells is discussed. (C) 1998 Federation of European Biochemical Societ ies.