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 results in cell clones devoid of telomerase activity. Azidothymidine and carbovir but not dideoxycytidine induce a process resembling aging in the immortal mouse fibroblast culture. As the cell proliferation is slowed down, large cells appear and their amount increases. Finally, proliferation ceases, and nondividing cells survive for a long time in culture. Cancellation of the reverse transcriptase inhibitors results in restoration of DNA synthesis in culture followed by appearance of mitotic cells, including giant ones containing over 600 chromosomes. Carbovir-resistant cells with very high telomerase activity were obtained upon long-term cultivation in the presence of the drug. These data allow us to think that azidothymidine and carbovir block the telomerase function in immortal mouse fibroblasts.