DNA Repair and the Carrier Ligand Specificity of Platinum Resistance

  • Stephen G. Chaney
  • Edward L. Mamenta


The major mechanisms of platinum resistance at the DNA level appear to be enhanced DNA repair and increased tolerance of Pt-DNA adducts. It is clear that enhanced repair activity, as measured by removal of Pt-DNA adducts from genomic DNA, is observed in a great many platinum-resistant cell lines (1–3). This enhanced removal of Pt-DNA adducts most likely represents an increase in nucleotide excision repair capacity (4), since that is the only repair process which has been shown to remove Pt-DNA adducts. Furthermore, those cell lines with defects in nucleotide excision repair show enhanced sensitivity to platinum complexes (5,6). Recent research has defined the enzymes needed for nucleotide excision repair (7). However, it is not yet clear which of these enzymes are limiting for nucleotide excision repair in vivo and are, therefore, increased in amount and/or activity in cisplatin-resistant cell lines. For example, Dabholkar et al. (8,9) have reported increased expression of ERCC1 and XPAC in tissue from patients who were resistant to cisplatin chemotherapy. However, both Katz et al. (10) and Sheibani and Eastman (11) have found no increased expression of ERCC1 in cisplatin-resistant cell lines. Similarly, we have found no increased expression or cisplatin-inducibility of XPAC in cisplatin-resistant cell lines (Vaisman et al., manuscript in preparation).


Nucleotide Excision Repair Platinum Complex DHFR Gene Human Ovarian Carcinoma Cell Line Nucleotide Excision Repair System 
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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Stephen G. Chaney
    • 1
  • Edward L. Mamenta
    • 1
  1. 1.Department of Biochemistry and Biophysics, Lineberger Comprehensive, Cancer Center and Curriculum in ToxicologyUniversity of North CarolinaChapel HillUSA

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