TOPOISOMERASE-I IN MULTIPLE-DRUG RESISTANCE

Topoisomerase I is a nuclear enzyme able to catalyse the relaxation of supercoiled DNA by introducing single-stranded breaks in DNA molecule . Its function seems important to prepare DNA for many processes such as recombination, DNA repair and RNA transcription. The most important drugs active as inhibitors of topoisomerase I are represented by camp tothecin and its derivatives which were developed as promising antican cer drugs. Since selectivity of action is essential for an antitumor d rug, many studies were performed to investigate the mechanisms by whic h cancer cells become resistant to drug treatment by developing a cond ition of multiple drug resistance (MDR). This article analyses the rol e of topoisomerase I in cell functions, considers the cellular effects of topo I poisons and discusses the ways by which tumoral cells may b ecome resistant to these drugs with a special attention to MDR mechani sms.