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

Abstract

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.

• Authors: Ho Yee Chan, Huan Wang, Lai K Leung
• Journal: The British journal of nutrition (Br J Nutr) Vol. 90 Issue 1 Pg. 87-92 (Jul 2003) ISSN: 0007-1145 [Print] England
• PMID: 12844379 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 9,10-Dimethyl-1,2-benzanthracene (metabolism)
• Animals
• Antimutagenic Agents (therapeutic use)
• Aryl Hydrocarbon Hydroxylases (antagonists & inhibitors, genetics)
• Biotransformation
• Carcinogens (metabolism)
• Cytochrome P-450 CYP1A1 (antagonists & inhibitors, 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)