TELOMERASE ACTIVITY AND TELOMERE LENGTHS IN VARIOUS CELL-LINES - CHANGES OF TELOMERASE ACTIVITY CAN BE ANOTHER METHOD FOR CHEMOSENSITIVITY EVALUATION

For the cancer cells which have overcome the second mitotic clock (M2) , activated telomerase is essential and used as another marker of immo rtality. Many trials had been initiated to target telomerase, which is known to be specific to tumors. To determine the best in vitro cell s ystem for testing the efficacy of telomerase inhibitors, we evaluated the telomerase activity of various cancer cell lines and measured thei r telomere lengths. We also treated some cancer cell lines with adriam ycin and measured the changes of telomerase activity. Telomerase activ ity was evaluated in various cell lines with the TRAP (telomeric repea t amplification protocol) assay. Telomerase activity was calculated an d translated into arbitrary units by computer-assisted densitometry wi th the control of telomerase activity in the 293 control cell line. Al so, terminal restriction fragment lengths were measured using Southern blotting. We also measured telomerase activity and telomere lengths i n 11 benign breast tumor tissues and 19 paired stomach cancer and norm al tissues. Cancer cell lines treated with adriamycin we evaluated for changes of telomerase activity and the cell proliferation by MTT assa y and dye exclusion test. Telomerase activity of cell lines was 95.3+/ -24.1 unit with a range of 27.6-129.6 unit, while the telomere lengths of those cell lines were variable from 5.0 to 10.4 kbp with a median of 6 kbp. In 11 cancer cell lines which were not yet firmly establishe d, we could not detect any telomerase activity. Low telomerase activit y was detected in only 2 benign tumor tissues of breast with a median telomere length of 8.8 (7-10.5) kbp. Among paired 19 gastric cancer an d normal tissues, only 7 cancer tissues showed weak telomerase activit y. After adriamycin treatment, telomerase activity in YCC-S-1, YCC-S-3 , MCF-7 and MCF-7/ADR was decreased in accordance with the changes of the cell numbers. Telomerase is specific to cancer tissues and is expr essed differently from organ to organ. Telomerase activity by TRAP ass ay could be used as a chemosensitivity assay.