TOPOISOMERASE-I GENE-EXPRESSION AND CELL SENSITIVITY TO CAMPTOTHECIN IN HUMAN CELL-LINES OF DIFFERENT TUMOR TYPES

Topoisomerase I (topo I) gene expression and cell sensitivity to campt othecin were investigated in seven human cancer cell lines not selecte d in vitro for drug resistance. The cell lines were of different tumor origin, and included two ovarian carcinomas (A2760 and IGROV-1), a ce rvix squamous cell carcinoma (A431), an osteosarcoma (U2-OS), a gliobl astoma (GBM) and two different clones of a malignant melanoma (685/2/6 0 and 665/2/21). Topo I gene expression was evaluated by Northern blot ting analysis and cell sensitivity to camptothecin was determined usin g the colony-forming assay after a 1 h exposure to the drug. A wide ra nge of drug sensitivity levels was found among the examined cell lines . Cell doubling times and distribution in cell cycle phases were not c orrelated with camptothecin cytotoxicity. In particular, the percent o f untreated cells in S phase was not predictive of the drug sensitivit y. No correlation was found between level of topo I gene expression an d cell response to camptothecin. These results indicate that the level of topo I expression is not the only critical determinant of cell sen sitivity to camptothecin in unselected human cancer cell lines. Theref ore, topo I gene expression may not be a useful predictive parameter o f tumor response.