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 mM. The comet assay indicated that DMBA introduced DNA damage to these cells, and co-treatment with genistein at 5 or 10 mM 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 mM-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) .Cytochrome P450 (CYP) 1A1 and CYP1B1 enzymes are responsible for the biotransformation of procarcinogens to genotoxic moieties PAH (3,4) . The importance of these CYP1 enzymes in PAH-induced carcinogenesis is implicated in two gene-knockout mouse results; benzo[a ]pyrene cannot induce CYP1A1 or cancer in aryl hydrocarbon receptor-null mice (5) , and lower cancer incidence was observed in 7,12-dimethyl-benz[a ]anthracene (DMBA)-treated CYP1B1 knockout mice (6) .The significance of the family of CYP1 enzymes in human breast cancer is not clear. Both tumour and normal tissues of the breast express CYP1A1 and CYP1B1 (7 -9) . The inhibition of CYP1 enzymes appears to be beneficial in the prevention of DMBA -DNA adduct formation in vivo (10) and in vitro (11) . Polymorphisms with higher activity of CYP1A1 appear to be a risk factor for breast cancer in African-Americans (12) ; so are the polymorphisms of CYP1B1 in Asian women (13) .Breast cancer is one of the most prevalent cancers in women. Asian countries have lower breast cancer incidences than the West; however, no difference in breast cancer incidence is found between Asian descendents and other women in America (14) . These observations suggest that environment may play a part in the aetiology of breast cancer, and soya consumption has been one of the major l...

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Polycyclic aromatic hydrocarbons (PAH) are procarcinogens that can be commonly found in our food and environment. Upon biotransformation in our body system, they can cause DNA damage through the generation of genotoxic species and oxidative stress. Phase I and II enzymes are pivotal in the process of proximate carcinogen formation and elimination. Some dietary phytochemicals are strong inhibitors to the phase I enzymes. In the present study, we investigated the effect of the red wine compound resveratrol on DNA damage induced by PAH in a non-tumorigenic breast cell line MCF-10A. Resveratrol ranging from 1 to 5 mM could significantly suppress the expressions of cytochrome P450 (CYP) 1A1, CYP1B1 and UDP-glucuronosyltransferase (UGT) 1A1 induced by 7,12-dimethylbenz[a ]anthracene (DMBA). The comet assay indicated that DMBA introduced DNA damage to these cells, and co-treatment of resveratrol at 5 or 10 mM could alleviate the damage. Further investigation illustrated that resveratrol reduced the binding of DMBA metabolites to DNA with no effect on DMBA-induced oxidative DNA damage. Since the phase II enzyme UGT1A1 was suppressed, the elimination of DMBA metabolites would not have contributed to the reduction in the DMBA metabolite-DNA binding. In summary, resveratrol might protect breast cells against PAH-induced DNA damage. The underlying mechanism was mediated by phase I enzyme suppression rather than phase II enzyme induction or oxidative DNA repair.