The red clover (Trifolium pratense) isoflavone biochanin A modulates the biotransformation pathways of 7,12-dimethylbenz[a]anthracene

Br J Nutr. 2003 Jul;90(1):87-92. doi: 10.1079/bjn2003868.


Several flavonoids have shown their anti-carcinogenic effects in various models. The soyabean isoflavone genistein was demonstrated earlier in our laboratory to be an effective inhibitor of dimethylbenz[a]anthracene (DMBA)-induced DNA damage in MCF-7 cells by curbing cytochrome P450 (CYP) 1 enzymes. The red clover (Trifolium pratense) isoflavone biochanin A is a methylated derivative of genistein, and its anti-mutagenic effect in bacterial cells has been shown previously. Because of its protection against chemical carcinogenesis in an animal model, biochanin A was selected for testing in our established MCF-7 cell system. From the results obtained in the semi-quantitative reverse transcription-polymerase chain reaction and xenobiotic response element (XRE)-luciferase reporter assays, biochanin A could reduce xenobiotic-induced CYP1A1 and -1B1 mRNA abundances through the interference of XRE-dependent transactivation. Enzyme kinetic studies also indicated that biochanin A inhibited both CYP1A1 and -1B1 enzymes with inhibition constant (Ki) values 4.00 and 0.59 microm respectively. Since the biotransformation of DMBA was dependent on CYP1 enzyme activities, biochanin A was able to decrease the DMBA-DNA lesions. The present study illustrated that the red clover isoflavone could protect against polycylic aromatic hydrocarbon-induced DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / metabolism*
  • Animals
  • Antimutagenic Agents / therapeutic use*
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors*
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Biotransformation
  • Carcinogens / metabolism*
  • Cytochrome P-450 CYP1A1 / antagonists & inhibitors*
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1B1
  • DNA Adducts / metabolism
  • Genistein / therapeutic use*
  • Luciferases / metabolism
  • RNA, Messenger / analysis
  • Response Elements
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured / metabolism


  • Antimutagenic Agents
  • Carcinogens
  • DNA Adducts
  • RNA, Messenger
  • 9,10-Dimethyl-1,2-benzanthracene
  • Genistein
  • Luciferases
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1B1
  • biochanin A