REVERSE-TRANSCRIPTASE INHIBITORS SUPPRESS TELOMERASE FUNCTION AND INDUCE SENESCENCE-LIKE PROCESSES IN CULTURED MOUSE FIBROBLASTS

Spontaneous transformation of mouse embryonic fibroblasts in the prese nce of the reverse transcriptase inhibitors azidothymidine and carbovi r led to the formation of telomerase-free clones, After prolonged cult ivation of fibroblasts in the presence of carbovir, resistant cells wi th a very high level of telomerase activity were obtained, Azidothymid ine and carbovir, but not dideoxycytidine, induced senescence-like pro cesses in cultures of immortal mouse fibroblasts, After long-term incu bation, cell proliferation gradually decreased, their morphology becom ing 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.