NO ALTERATION IN DNA TOPOISOMERASE-I GENE-RELATED TO CPT-11 RESISTANCE IN HUMAN LUNG-CANCER

Mutations and reduced expression of DNA topoisomerase I (topo I) gene have been shown to be important in the acquisition of resistance to ca mptothecin and its analogues in vitro, but their significance has not been verified in vivo. We investigated possible topo I gene mutations and topo I mRNA expression levels in 127 samples obtained from 56 pati ents with lung tumors, including patients who had developed clinical r esistance to topo I inhibitors. No mutations were detected in any of t he samples examined and expression levels did not differ significantly between clinically resistant cases and others. However, the topo I mR NA expression level was significantly higher in small cell lung carcin omas than in non-small cell lung carcinomas (P< 0.05). These results s uggest that topo I mRNA levels may affect CPT-11 sensitivity in human lung cancer. However, topo I gene mutations and reduced topo I mRNA ex pression may not be the main mechanism of clinically acquired resistan ce to camptothecin analogues in vivo.