Reverse transcriptase inhibitors suppress telomerase function and induce senescence-like processes in cultured mouse fibroblasts.
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.
Yegorov
Y E
YE
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation.
Chernov
D N
DN
Akimov
S S
SS
Bolsheva
N L
NL
Krayevsky
A A
AA
Zelenin
A V
AV
D016475:3T3 Cells; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D015224:Dideoxynucleosides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology / Q000821:virology; D051379:Mice; D008808:Mice, Inbred CBA; D008938:Mitosis / Q000187:drug effects; D008969:Molecular Sequence Data; D011123:Polyploidy; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013539:Simian virus 40 / Q000235:genetics; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology*
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; C057503:carbovir; D015215:Zidovudine; D019098:Telomerase