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DNA Repair and the Carrier Ligand Specificity of Platinum Resistance

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Book cover Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy 2

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Abstract

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).

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Lineberger Comprehensive, Cancer Center and Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC, 27599-7260, USA

    Stephen G. Chaney & Edward L. Mamenta

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  1. Stephen G. Chaney
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  1. Free University, Amsterdam, The Netherlands

    H. M. Pinedo

  2. Netherlands Cancer Institute, Amsterdam, The Netherlands

    J. H. Schornagel

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Chaney, S.G., Mamenta, E.L. (1996). DNA Repair and the Carrier Ligand Specificity of Platinum Resistance. In: Pinedo, H.M., Schornagel, J.H. (eds) Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0218-4_31

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