Gemcitabine causes minimal modulation of carboplatin-DNA monoadduct formation and repair in bladder cancer cells

Chem Res Toxicol. 2010 Nov 15;23(11):1653-5. doi: 10.1021/tx1003547. Epub 2010 Oct 28.

Abstract

We are developing a method to identify cellular resistance to carboplatin by using accelerator mass spectrometry to measure carboplatin-DNA adducts formed from drug microdoses (∼1/100th the therapeutic dose). Such an approach would be particularly useful if it is still valid in combination chemotherapy. We examined whether the addition of gemcitabine, another chemotherapeutic drug, could influence carboplatin-DNA adduct levels. There were no substantial differences in the levels of carboplatin-DNA adducts in cells upon exposure to the carboplatin/gemcitabine combination at various doses and schedules. These data demonstrate that microdosing is feasible for the characterization of carboplatin resistance when given in combination with gemcitabine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / toxicity*
  • Carboplatin / administration & dosage
  • Carboplatin / analysis
  • Carboplatin / chemistry
  • Carboplatin / therapeutic use
  • Carboplatin / toxicity*
  • Cell Line, Tumor
  • DNA Adducts / analysis*
  • DNA Adducts / chemistry
  • DNA Repair*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Deoxycytidine / toxicity
  • Drug Resistance, Neoplasm
  • Gemcitabine
  • Humans
  • Urinary Bladder Neoplasms / drug therapy*

Substances

  • DNA Adducts
  • carboplatin-DNA adduct
  • Deoxycytidine
  • Carboplatin
  • Gemcitabine