Reverse transcriptase inhibitors suppress telomerase function and induce senescence‐like processes in cultured mouse fibroblasts

Abstract

Spontaneous transformation of mouse embryonic fibroblasts in the presence of the reverse transcriptase inhibitors azidothymidine and carbovir led to the formation of telomerase‐free clones. After prolonged cultivation of fibroblasts in the presence of carbovir, resistant cells with a very high level of telomerase activity were obtained. Azidothymidine and carbovir, but not dideoxycytidine, induced senescence‐like processes in cultures of immortal mouse fibroblasts. After long‐term incubation, cell proliferation gradually decreased, their morphology becoming similar to that of the senescent ones. The process was reversible: after inhibitor removal, the cells, including the giant ones, entered mitoses. All these data suggest that reverse transcriptase inhibitors block telomerase function in mouse cells.