Blockade of telomerase function in various cells

The reverse transcriptase inhibitors (RTI) azidothymidine and carbovir can block telomerase function in various cells, whereas dideoxycytidine does no t exhibit such activity. RTI induce senescence in 3T3 Swiss, NIH 3T3 cell c ultures and in the clones of immortal spontaneously transformed mouse fibro blasts. The RTI-induced senescence of L6 rat myoblasts in culture resembles the senescence of fibroblasts, but the resulting cells acquire sharp morph ological peculiarities. The artificial senescence of fibroblasts and myobla sts resulted in both the appearance of corresponding senescent cells and a small portion of cells with the signs of another type of differentiation, T he blockade of telomerase function by RTI in the human tumour cell lines U- 937 and MeWo leads to the shortening of telomeres, but does not result in s enescence. These cells may undergo crisis and after a while the proliferati on resumes and resistant cells appear. RTI inhibit spontaneous reactivation of telomerase in the process of spontaneous transformation of mouse embryo nic fibroblasts, which leads to the formation of telomerase-free clones. A fraction of these clones may overcome the senescence via the acquisition of telomerase activity. Cells with a very high level of telomerase activity b ecome resistant to RTI, Thus, the blockade of telomerase function in differ ent cells can induce senescence, partial differentiation or crisis. In huma n tumour cells it induces mainly crisis.