INHIBITION OF HUMAN TUMOR-CELL PROLIFERATION BY ANALOGS OF ADENOSINE

The effects of adenosine and several structural analogues of adenosine upon thymidine incorporation into human tumour cells and rat cervical lymphocytes were investigated. The analogue NECA, which has equal spe cificity for the A(1) and A(2) receptor, had the most inhibitory effec t on lymphocyte proliferation while the A(1) agonists had limited effe cts, suggesting that these cells possess principally A(2) adenosine re ceptors. In the case of human tumour cells, however, the most inhibito ry effect on proliferation was obtained with the A(1)-specific analogu es. The general order of inhibitory effects of adenosine analogues on thymidine incorporation in human tumour cells was: S-ENBA > CPA = R-PI A > S-PIA > NECA. These findings suggest that in the cells presently s tudied the A(1) adenosine receptor predominates. Removal of exogenous adenosine by growth in the presence of adenosine deaminase inhibited t hymidine incorporation. The effect of adenosine removal lends further support to the proposal that adenosine has some, as yet unidentified, regulatory role in the control of human tumour cell proliferation. (C) 1997 by John Wiley & Sons, Ltd.