PMID:8827012

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Citation

Chaney, SG and Sancar, A (1996) DNA repair: enzymatic mechanisms and relevance to drug response. J. Natl. Cancer Inst. 88:1346-60

Abstract

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 repair 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 this review, we examine the types of DNA adducts formed by the major classes of chemotherapeutic agents, the enzymatic pathways that play a role in the repair of those adducts, the evidence that DNA repair is enhanced in drug-resistant cell lines and tumors, and strategies for utilizing selective inhibition of DNA repair to overcome resistance.

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Keywords

Animals; Antineoplastic Agents/pharmacology; DNA Adducts/drug effects; DNA Adducts/metabolism; DNA Repair/drug effects; Drug Resistance, Neoplasm; Humans; Neoplasms/drug therapy; Neoplasms/physiopathology

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