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Intercalation and induction of strand breaks by adriamycin and daunomycin: a study with human genomic DNA

Debjani Ghosh1, Maidul Hossain, Chabita Saha

  • 1School of Biotechnology and Biological Sciences, West Bengal University of Technology, Salt Lake, Kolkata, India.

DNA and Cell Biology
|August 19, 2011
PubMed

Insights

Adriamycin (ADR) and Daunomycin (DNM) are effective anticancer drugs. Their DNA intercalation efficiency does not directly correlate with DNA strand breaks or genotoxicity, which is linked to reactive oxygen species.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Genetics

Background:

  • Adriamycin (ADR) and Daunomycin (DNM) are anthracycline anticancer drugs.
  • DNA intercalation is believed to be essential for their cytotoxic activity.
  • The relationship between DNA intercalation and cytotoxicity-linked cellular processes remains unclear.

Purpose of the Study:

  • To investigate the relationship between DNA intercalation and DNA strand breaks induced by ADR and DNM.
  • To assess the genotoxicity of ADR and DNM in human lymphocytes.
  • To explore the correlation between intercalation efficiency, genotoxicity, and reactive oxygen species production.

Main Methods:

  • Absorption and fluorimetric methods were used to assess DNA intercalation.
  • Thermal melting temperature and circular dichroic spectral changes were analyzed.
  • Single cell gel electrophoresis (SCGE; comet assay) was employed to measure DNA strand breaks and genotoxicity.

Main Results:

  • ADR and DNM were confirmed as strong intercalators of human genomic DNA, with DNM being a more potent intercalator.
  • Both drugs induced equivalent genotoxicity in normal human lymphocytes at clinically relevant doses.
  • The observed genotoxicity was independent of intercalation efficiency but positively correlated with reactive oxygen species yield.

Conclusions:

  • DNA intercalation efficiency does not solely determine the genotoxicity of ADR and DNM.
  • Reactive oxygen species play a significant role in the genotoxic effects of these anthracycline drugs.
  • Further research is needed to fully elucidate the mechanisms of ADR and DNM cytotoxicity.

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