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

Published online by Cambridge University Press:  07 June 2007

Ho Yee Chan ,
Huan Wang  and
Lai K. Leung
Ho Yee Chan
Affiliation:
Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong
Huan Wang
Affiliation:
Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong
Lai K. Leung*
Affiliation:
Food and Nutritional Sciences Programme, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong
*
*Corresponding author: Dr Lai K. Leung, fax +852 2603 7732, email laikleung@yahoo.com
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Abstract

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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 0·59μM 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.

Keywords

Biochanin ACytochrome P450 1A1Cytochrome P450 1B17,12-Dimethylbenz[a]anthracene–DNA lesion
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 1 , July 2003 , pp. 87 - 92
Copyright
Copyright © The Nutrition Society 2003

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