Role of recombinant human erythropoietin in mitomycin C-induced genotoxicity: analysis of DNA fragmentation, chromosome aberrations and micronuclei in rat bone-marrow cells

Mutat Res. 2013 Apr 30;753(1):48-53. doi: 10.1016/j.mrgentox.2012.12.011. Epub 2013 Jan 30.

Abstract

Mitomycin C (MMC) is one of the most effective chemotherapeutic agents. However, during clinical use several side effects may occur. Recombinant human erythropoietin (rhEPO), a glycoprotein that regulates haematopoiesis, has been shown to exert an important cyto-protective effect in many tissues. The aim of this study was to explore whether rhEPO protects against MMC-induced genotoxicity in rat bone-marrow cells. Adult male Wistar rats were divided into six groups of 18 animals each: a control group, a 'rhEPO alone' group, an 'MMC alone' group and three 'rhEPO+MMC' groups (pre-, co- and post-treatment conditions). Our results show that MMC induced a noticeable genotoxic effect in rat bone-marrow cells. rhEPO reduced the effects of MMC significantly in every type of experiment conducted, such as the frequency of micronuclei, the percentage of chromosome aberrations and the level of DNA damage measured with the comet assay. The protective effect of rhEPO was more efficient when it was given 24h prior to MMC treatment.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / antagonists & inhibitors*
  • Alkylating Agents / toxicity
  • Animals
  • Antimutagenic Agents / administration & dosage
  • Antimutagenic Agents / pharmacology
  • Antimutagenic Agents / therapeutic use*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / ultrastructure
  • Chromosome Aberrations / drug effects*
  • DNA Fragmentation / drug effects*
  • Drug Administration Schedule
  • Drug Evaluation, Preclinical
  • Epoetin Alfa
  • Erythropoietin / administration & dosage
  • Erythropoietin / pharmacology
  • Erythropoietin / therapeutic use*
  • Male
  • Micronuclei, Chromosome-Defective / drug effects*
  • Micronucleus Tests
  • Mitomycin / antagonists & inhibitors*
  • Mitomycin / toxicity
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use

Substances

  • Alkylating Agents
  • Antimutagenic Agents
  • Recombinant Proteins
  • Erythropoietin
  • Mitomycin
  • Epoetin Alfa