DNA-REPAIR - ENZYMATIC MECHANISMS AND RELEVANCE TO DRUG RESPONSE

A number of chemotherapeutic agents, such as platinum drugs, nitrogen mustards, and chloroethylnitrosoureas, act by forming bifunctional DNA adducts, It is likely that abortive attempts to replicate and/or repa ir the damaged DNA cause chromosome aberrations and breakage, leading to cell death, Any substantial increase in cellular capacity to repair damaged DNA may result in resistance to chemotherapeutic agents. In t his review, we examine the types of DNA adducts formed by the major cl asses of chemotherapeutic agents, the enzymatic pathways that play a r ole in the repair of those adducts, the evidence that DNA repair is en hanced in drug-resistant cell lines and tumors, and strategies for uti lizing selective inhibition of DNA repair to overcome resistance.