Telomerase activity and telomere length in human ovarian cancer and melanoma cell lines: Correlation with sensitivity to DNA damaging agents

Since telomerase plays a role in cellular resistance to apoptosis, which is the primary mode of cell death induced by several drugs, telomerase could be involved in determining the chemosensitivity profile of tumor cells. Thu s, we investigated the relationship between telomerase activity, telomere l ength and chemosensitivity to effective antitumor agents in a panel of huma n melanoma and ovarian cancer cell lines. Telomerase activity, as detected by the telomeric repeat amplification protocol, ranged fr om 0.58 to 1.10 a rbitrary units in individual cell lines, with similar median values for mel anoma and ovarian carcinoma cell lines (0.80 vs 0.90). Telomeres were gener ally longer in melanoma than in ovarian carcinoma cell lines, with a more t han 2-fold median telomere restriction fragment length (7.74 vs 3.82 kb). N o significant correlation was evidenced between the two telomere-related pa rameters and cell population doubling time, DNA index or TP53 gene status. No precise relation was found between telomerase activity and cellular sens itivity to different DNA damaging agents including doxorubicin, cisplatin a nd the multinuclear platinum compound BBR 3464. In contrast, longer telomer es were associated to resistance to the drugs, even though the association reached statistical significance only for cisplatin. Since platinum compoun ds may have affinity for telomere sequences, it is conceivable that the int eraction is relevant for drug sensitivity/resistance status depending on te lomere length.