Cell death in paclitaxel-dependent Chinese hamster ovary cells is initiated by the loss of telomeric DNA repeats

have reported earlier that cell death in a metastatic murine melanoma cell line induced by paclitaxel and its water-soluble conjugates is mediated thr ough the extensive erosion of telomeric repeats. The purpose of this study was to investigate if loss of telomeric repeats was also involved in cell d eath of Tax-18 and Tax-2-4, two paclitaxel-requiring mutant Chinese hamster ovary (CHO) cell lines. Tax-18 and Tax-2-4 cells were grown in paclitaxel- free culture medium for 24, 48, 72, and 96 h at 37 degrees C and then harve sted for cytological preparations. Control cultures of both cell lines were grown in paclitaxel-supplemented medium and harvested simultaneously. We f ound that: 1) the frequency of telomeric associations in metaphase preparat ions was increased with the duration of paclitaxel-depleted culture; 2) Tax -18 cells showed a higher incidence (33.0%) of endoreduplicated metaphases at 24 h of paclitaxel-depleted culture than did Tax-2-4 cells, in which end oreduplicated metaphases were rare; 3) the frequency of polyploid cells was increased after 48, 72, and 96 h of paclitaxel-depleted culture for Tax-18 relative to that for Tax-2-4 cells; 4) both cell lines showed reductions i n telomeric signals at chromosomal termini, but not in the interphase nucle i; and 5) both cell lines had shorter terminal telomeric restriction fragme nts after culture in paclitaxel-depleted medium. These results support our earlier observations and indicate that reduction of telomeric repeats is in volved in G(2)/M cell arrest (endoreduplication) followed by severe DNA fra gmentation, and then cell death of two CHO mutant cell lines that require p aclitaxel for cell division.