Sg. Chaney et A. Sancar, DNA-REPAIR - ENZYMATIC MECHANISMS AND RELEVANCE TO DRUG RESPONSE, Journal of the National Cancer Institute, 88(19), 1996, pp. 1346-1360
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.