EFFECT OF REVERSE-TRANSCRIPTASE INHIBITORS ON TELOMERASE FUNCTION IN IMMORTAL MOUSE FIBROBLASTS

Spontaneous transformation of mouse embryo fibroblasts in the presence of reverse transcriptase inhibitors azidothymidine or carbovir result s in cell clones devoid of telomerase activity. Azidothymidine and car bovir but not dideoxycytidine induce a process resembling aging in the immortal mouse fibroblast culture. As the cell proliferation is slowe d down, large cells appear and their amount increases. Finally, prolif eration ceases, and nondividing cells survive for a long time in cultu re. Cancellation of the reverse transcriptase inhibitors results in re storation of DNA synthesis in culture followed by appearance of mitoti c cells, including giant ones containing over 600 chromosomes. Carbovi r-resistant cells with very high telomerase activity were obtained upo n long-term cultivation in the presence of the drug. These data allow us to think that azidothymidine and carbovir block the telomerase func tion in immortal mouse fibroblasts.