Genistein protects against polycyclic aromatic hydrocarbon-induced oxidative DNA damage in non-cancerous breast cells MCF-10A
| Autor: | A.-Lien Lu, Lai Hang Yung, Ching Ho Poon, Lai K. Leung, Guoli Shi, Hau Y. Leung |
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| Rok vydání: | 2008 |
| Předmět: |
DNA damage
DNA repair 9 10-Dimethyl-1 2-benzanthracene Gene Expression Medicine (miscellaneous) DMBA Genistein Cell Line chemistry.chemical_compound Cytochrome P-450 CYP1A1 polycyclic compounds Anticarcinogenic Agents Humans Breast Polycyclic Aromatic Hydrocarbons Carcinogen Air Pollutants Nutrition and Dietetics Reverse Transcriptase Polymerase Chain Reaction Mutagenesis food and beverages Flow Cytometry Comet assay Oxidative Stress chemistry Biochemistry Cytochrome P-450 CYP1B1 Female Aryl Hydrocarbon Hydroxylases Comet Assay DNA DNA Damage |
| Zdroj: | British Journal of Nutrition. 101:257-262 |
| ISSN: | 1475-2662 0007-1145 |
| Popis: | 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 5mM. The comet assay indicated that DMBA introduced DNA damage to these cells, and co-treatment with genistein at 5 or 10mM 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 10mM-genistein. Because no increased oxidative DNA repair was observed, suppression on the cytochrome enzymes appeared to be the underlying mechanism. Cytochrome P450: Comet assay: 8-Oxo-guanine: Genistein Polycyclic aromatic hydrocarbons (PAH) are commonly found in our environment, and they can be isolated from diesel exhaust, barbequed meat, tobacco smoke, overheated cooking oil, etc (1) . PAH are metabolised and transformed into DNAattacking electrophiles in the body. The significance of these environmental toxicants in breast cancer can be inferred from the increased presence of PAH‐DNA adducts in human breast tumours (2) . |
| Databáze: | OpenAIRE |
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