Evaluation of mutagenic activity of platinum complexes in somatic cells of Drosophila melanogaster

Food Chem Toxicol. 2019 Nov:133:110782. doi: 10.1016/j.fct.2019.110782. Epub 2019 Aug 26.

Abstract

Cisplatin, carboplatin, and oxaliplatin are some of the most often used alkylating chemotherapeutic agents. In view of the paucity of data on the genotoxicity of oxaliplatin, this study compares the mutagenic activity of cisplatin (0.006, 0.012, 0.025, 0.05 mM), carboplatin (0.1, 0.2, 0,5, 1.0 mM), and oxaliplatin (0.1, 0.2, 0,5, 1.0 mM) using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Standard and high-bioactivation crosses of the drosophilid were used, which present basal and high levels of cytochrome P450 (CYP450) metabolization enzymes, respectively. All concentrations of cisplatin and carboplatin induced lesions in genetic material in both crosses, while oxaliplatin was mutagenic only to high bioactivation flies treated with 0.1, 0.5 and 1 mM of the compound. No significant differences were observed between genotoxicity values of cisplatin and carboplatin. However, CYP450 enzymes may have affected the mutagenic action of oxaliplatin. Carboplatin induced mainly mutation events, while cisplatin triggered mostly mutation and recombination events when low and high doses were used. Most events induced by oxaliplatin were generated by somatic recombination. Important differences were observed in genotoxic potential of platinum chemotherapeutic compounds, possibly due to the origin and type of the lesions induced in DNA and the repair mechanisms involved.

Keywords: Carboplatin; Cisplatin; Mutation; Oxaliplatin; Somatic recombination.

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Carboplatin / toxicity*
  • Cisplatin / toxicity*
  • DNA Damage / drug effects
  • Drosophila melanogaster / drug effects*
  • Drosophila melanogaster / genetics
  • Female
  • Male
  • Mutagenesis / drug effects
  • Mutagenicity Tests
  • Mutagens / toxicity*
  • Mutation / drug effects
  • Oxaliplatin / toxicity*
  • Recombination, Genetic / drug effects

Substances

  • Antineoplastic Agents
  • Mutagens
  • Oxaliplatin
  • Carboplatin
  • Cisplatin