DECLINE IN TELOMERASE ACTIVITY AS A MEASURE OF TUMOR-CELL KILLING BY ANTINEOPLASTIC AGENTS IN-VITRO

Telomerase activity is frequently associated with the malignant phenot ype, and it can be considered an almost ubiquitous tumor marker, In th is study, we evaluated telomerase activity in telomerase-positive huma n tumor cell lines exposed in vitro to antineoplastic agents, The resu lts show that drug-induced cell killing of tumor cells is associated w ith a decline in detectable telomerase activity, The decrease of telom erase activity levels paralleled cell growth impairment evaluated by c ell count or by measurement of cell ability to convert tetrazolium sal t to colored formazan (4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazoli um bromide assay], The observed telomerase activity remaining after tr eatment with antineoplastic agents is most likely to reflect activity from the remaining viable cells, When tumor cell lines resistant to th e chemotherapeutic agents temozolomide or doxorubicin were treated wit h these compounds, no decline of telomerase activity or cell growth wa s observed. The results of the present study indicate that resistance of neoplastic cells to chemotherapeutic agents can be monitored by fol lowing telomerase activity, Moreover, the test can be performed with a limited number of neoplastic cells, such as those frequently obtained from tumor biopsies, These findings provide a rationale for developin g new in vitro chemosensitivity assays, and detection of telomerase ac tivity may be a novel marker of chemotherapy failure.