In vitro and in vivo inhibition of telomerase activity from Chinese hamster V79 cells

While studying the inhibition of telomerase activity in Chinese hamster V79 cells using polymerase chain reaction (PCR) based telomeric repeat amplifi cation protocol (TRAP) assay, we had earlier observed that 7-deaza deoxy gu anosine triphosphate (7-deaza dGTP) and oligonucleotide (TTAGGG)(4) inhibit ed telomerase activity in vitro. In the present study, we report inhibition of telomerase activity by modified base 7-deaza deoxy adenosine triphospha te (7-deaza dATP) and phosphorothioate TTAGGG (PS-TTAGGG). Both the compoun ds inhibited telomerase activity in a concentration dependent manner; 8.5 m uM of 7-deaza dATP and 0.1 muM of PS-TTAGGG being the concentration for 50% of the minimum inhibition. This observation supports our earlier hypothesi s that incorporation of a modified nucleotide into telomere possibly interf eres with the recognition of the telomerase and TTAGGG interferes with the RNA component of telomerase. We have further shown that treatment of cells with nicotinamide (NA) and benzamide (BA), well known inhibitors of poly (A DP-ribose) polymerase, reduced telomerase activity. We speculate that modif ication of the telomeric binding proteins or other components by poly (ADP- ribosyl)ation may be involved in such inhibition.