Genotoxicity of the isoflavones genistein, daidzein and equol in V79 cells

Toxicol Lett. 2004 Jun 15;151(1):151-62. doi: 10.1016/j.toxlet.2004.04.005.


Hormonally active chemicals in the human diet, such as man-made estrogenic chemicals or plant-derived compounds (phytoestrogens), have become a matter of public concern. A significant part of human exposure to phytoestrogens is attributable to soy isoflavones. Besides their estrogenic properties, soy isoflavones also exert genotoxic actions. In this paper, the micronucleus (MN) assay in V79 cells was used to study chromosomal genotoxicity. Genistein caused a clear dose-related induction of MN within the range of 5-25 microM; MN rates were declining at higher genistein concentrations. This was probably due to cytotoxicity of genistein since reduced neutral red uptake and MTT formation with an IC(50) of about 75 microM occurred. Daidzein induced a comparatively shallow increase in the number of MN between 25 and 100 microM. In contrast, the daidzein metabolite equol caused an increase in the number of MN up to 25 microM with no further increase at higher concentrations. Additional staining with anti-kinetochore (CREST) antibodies served to determine if the micronuclei contain whole chromosomes or acentric fragments. Genistein induced mostly CREST(-) micronuclei, i.e. MN with chromosomal fragments, thus indicative of a clastogenic mode of action. MN induced by high concentrations of daidzein were partly CREST(+) and CREST(-), whilst equol induced mostly CREST(+) micronuclei indicative of an aneugenic action. These results point to a differential genotoxicity of phytoestrogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / toxicity*
  • Benzothiazoles
  • Coloring Agents / metabolism
  • Comet Assay
  • Cricetinae
  • Cricetulus
  • DNA Damage*
  • Dose-Response Relationship, Drug
  • Equol
  • Fibroblasts / metabolism
  • Formazans / metabolism
  • Genistein / metabolism
  • Genistein / toxicity*
  • Isoflavones / metabolism
  • Isoflavones / toxicity*
  • Micronucleus Tests
  • Neutral Red / metabolism
  • Sulfonic Acids / metabolism
  • Tetrazolium Salts / metabolism


  • 4',7-dihydroxy-3,4-dihydroisoflavone
  • Antineoplastic Agents
  • Benzothiazoles
  • Coloring Agents
  • Formazans
  • Isoflavones
  • Sulfonic Acids
  • Tetrazolium Salts
  • MTT formazan
  • Neutral Red
  • 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid
  • Equol
  • daidzein
  • Genistein