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A potential protective mechanism of soya isoflavones against 7,12-dimethylbenz[a]anthracene tumour initiation

Published online by Cambridge University Press:  09 March 2007

Ho Yee Chan
Affiliation:
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong
Lai K. Leung*
Affiliation:
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong
*
*Corresponding author: Dr Lai K. Leung, fax +852 26037732, email laikleung@yahoo.com
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Abstract

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Epidemiological studies indicate that Asian women have a lower breast cancer incidence compared with their counterparts in the West, and the difference has been related to soya consumption. Animal studies have suggested that soya may prevent dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in the breast. In the present study a cell culture model was developed to address the effect of soya isoflavones on the DMBA-induced DNA damage. DMBA is metabolized into a DNA-attacking moiety by two phase I cytochrome P450 (CYP) enzymes CYP1A1 and CYP1B1. DNA mutation caused by this genotoxic agent is a crucial step in cancer initiation. Substances that interfere with the CYP1 enzyme activities can affect the initiation. In the present study, genistein was found to be an effective inhibitor of recombinant human CYP1A1 and CYP1B1 with Ki of 15·35 and 0·68 μmol/l. The other soya isoflavone daidzein, on the other hand, did not demonstrate any significant inhibition of the enzyme activities. At the transcriptional level, DMBA induced the CYP1 enzyme expressions by stimulating the xenobiotic response element (XRE)-dependent transactivation pathway. When genistein (25 μmol/l) was co-administered with DMBA, the XRE-Luc activity the CYP1 mRNA abundances were significantly suppressed. The present study illustrated that the soya isoflavone genistein, but not daidzein, protected against DMBA genotoxicity.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2003

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