Volume 90, Issue 1, July (2003), pp. 87-92 © The Author 2003
doi:10.1079/BJN2003868

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

Lai K. Leung^1,2, Ho Yee Chan², Huan Wang^2
1Food and Nutritional Sciences Programme, Faculty of Science
²Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong

 (Received 30 September 2002–Revised 24 January 2003–Accepted 18 February 2003)

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 (K_i) values 4·00 and 0·59 μm 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 A, Cytochrome P450 1A1, Cytochrome P450 1B1, 7,12-Dimethylbenz[a]anthracene–DNA lesion

Abbreviations:
AHR, aryl hydrocarbon receptor, CYP, cytochrome P450, DMBA, 7,12-dimethyl benz[a]anthracene, EROD, ethoxyresorufin-O-deethylase, MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, PAH, polycyclic aromatic hydrocarbon, PCR, polymerase chain reaction, XRE, xenobiotic response element