Flavonoids inhibit genetic toxicity produced by carcinogens in cells expressing CYP1A2 and CYP1A1

S Lautraite1, A C Musonda, J Doehmer

  • 1School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.

Mutagenesis
|December 26, 2001
PubMed

Insights

Flavonoids quercetin, apigenin, and chrysin were tested for their effects on the genetic toxicity of IQ and BaP in cells expressing specific P450 enzymes. Quercetin inhibited IQ-induced DNA damage, while chrysin and apigenin inhibited BaP-induced damage.

Area of Science:

  • Biochemistry
  • Toxicology
  • Molecular Biology

Background:

  • Flavonoids are plant-derived compounds with potential health benefits.
  • Certain flavonoids can modulate the activity of cytochrome P450 enzymes.
  • Genetic toxicity of environmental mutagens like IQ and BaP is often mediated by P450 metabolism.

Purpose of the Study:

  • To investigate the modulatory effects of quercetin, apigenin, and chrysin on the genetic toxicity induced by IQ and BaP.
  • To determine the role of specific cytochrome P450 enzymes (CYP1A1 and CYP1A2) in mediating this toxicity and the inhibitory potential of these flavonoids.

Main Methods:

  • Chinese hamster V79 cells expressing human CYP1A1 (V79 h1A1-MZ) or rat CYP1A2 (V79 r1A2-NH) were used.
  • Genetic toxicity was assessed by measuring DNA strand breaks (Comet assay) and DNA adducts (32P-post-labelling).
  • Flavonoid effects were evaluated at sub-cytotoxic concentrations, and enzyme specificity was confirmed using ethylresorufin O-deethylase assays.

Main Results:

  • IQ and BaP induced DNA damage (strand breaks and adducts) only in cells expressing the respective P450 enzymes (CYP1A2 for IQ, CYP1A1 for BaP).
  • Quercetin significantly inhibited IQ-induced DNA damage in V79 r1A2-NH cells.
  • Chrysin and apigenin inhibited BaP-induced DNA damage in V79 h1A1-MZ cells, whereas quercetin did not.

Conclusions:

  • Quercetin specifically inhibits CYP1A2-mediated genotoxicity of IQ.
  • Chrysin and apigenin specifically inhibit CYP1A1-mediated genotoxicity of BaP.
  • These findings highlight the potential of specific flavonoids to mitigate the risks associated with exposure to certain environmental mutagens through P450 enzyme modulation.

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