Genistein protects against polycyclic aromatic hydrocarbon-induced oxidative DNA damage in non-cancerous breast cells MCF-10A.
Polycyclic aromatic hydrocarbons (PAH) are established cancer initiators that can be found in our food and environment. Some dietary phytochemicals are strong inhibitors of PAH-induced mutagenesis. The soya isoflavone genistein has been shown previously in our laboratory to be an inhibitor of PAH metabolite binding to DNA. In the present study, we investigated the effect of genistein on oxidative DNA damage induced by PAH in the non-tumorigenic breast cell line MCF10A. 7,12-Dimethyl-benz[a]anthracene (DMBA) can induce expressions of CYP1A1 and CYP1B1 which are known to be responsive to PAH. These enzymes, in turn, will metabolise the PAH into their ultimate carcinogenic forms. Genistein can significantly suppress the expressions within 5 microm. The comet assay indicated that DMBA introduced DNA damage to these cells, and co-treatment with genistein at 5 or 10 microm could alleviate the damage. In addition to the chelation of DMBA metabolites to DNA, flow cytometry results revealed that oxidation was also a factor of DNA damage. The oxidative DNA damage could be removed by co-treating with 10 microm-genistein. Because no increased oxidative DNA repair was observed, suppression on the cytochrome enzymes appeared to be the underlying mechanism.
Leung
Hau Y
HY
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Yung
Lai Hang
LH
Poon
Ching Ho
CH
Shi
Guoli
G
Lu
A-Lien
AL
Leung
Lai K
LK
D015127:9,10-Dimethyl-1,2-benzanthracene; D000393:Air Pollutants / Q000378:metabolism*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001940:Breast / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D020552:Comet Assay; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004249:DNA Damage; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D018384:Oxidative Stress; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000393:Air Pollutants; D016588:Anticarcinogenic Agents; D011084:Polycyclic Aromatic Hydrocarbons; D015127:9,10-Dimethyl-1,2-benzanthracene; D019833:Genistein; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1