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Lycopene and beta-carotene ameliorate catechol estrogen-mediated DNA damage
2005
Muzandu, K. (Hokkaido Univ., Sapporo (Japan)) | Bohi, K.E. | Shaban, Z. | Ishizuka, M. | Kazusaka, A. | Fujita, S.
The consumption of fruits and vegetables is associated with a reduced risk of various ailments, including cancer and cardiovascular diseases. Carotenoids, such as lycopene and beta-carotene, are natural constituents of edible plants and may protect against disease. In this study, the influence of lycopene and beta-carotene on DNA damage caused by catechol-estrogens in vitro is examined. One possible mechanism by which catechol estrogens such as 4- hydroxyestradiol (4-OHE2) and 2- hydroxyestradiol, which cause DNA damage in naked plasmid DNA as well as in cells, contributing to the process of carcinogenesis, is through the generation of reactive oxygen species. It was found that both carotenoids at concentrations ranging from 0.25 to 10 MicroM significantly inhibit strand breakage induced by 4- OHE2/copper sulphate by up to 90%in plasmid DNA with beta-carotene being slightly more effective. No pro-oxidant or cytotoxic effects were observed at the concentrations tested. These carotenoids had a similar, though reduced effect on DNA damage as measured by the comet assay, in Chinese hamster lung fibroblasts. The results obtained show that both lycopene and beta-carotene, most probably and mainly through their potent antioxidant properties, are able to inhibit catecholestrogen-mediated DNA damage.
Afficher plus [+] Moins [-]Antigenotoxic effect of Pleurotus cornucopiae extracts on the mutagenesis of Salmonella typhimurium TA98 elicited by benzo(a)pyrene and oxidative DNA lesions in V79 hamster lung cells
2005
Bohi, K.M.E. (Hokkaido Univ., Sapporo (Japan)) | Sabik, L. | Muzandu, K. | Shaban, Z. | Soliman, M. | Ishizuka, M. | Kazusaka, A. | Fujita, S.
Pleurotus cornucopiae (PC) mushroom with a brilliant yellow pileus is found in the field and known in Japan as Tamogi dake mushroom. The purpose of this paper is to investigate the mechanism of the antimutagenic effect of PC mushroom using both the Ames test and Comet assay. We have found a strong inhibitory effect of both aqueous and organic PC extracts on the mutagenicity elicited by benzo[a]pyrene (B[a]P). This inhibition was dose- dependent in reaction mixtures containing cytosolic and microsomal fractions (S-9) from untreated rat liver as well as in those containing S-9 from aryl hydrocarbon receptor (Au) ligand of Sudan III-treated rats. Sudan III was a potent inducer of cytochrome P450 1A (CYP1A) activity. We treated rats with Sudan III to enhance the metabolic activation of B[a]P by the S-9 fraction. To explain whether this antimutagenicity was due to the inhibition of CYP1A activity that metabolically activates B[a]P, we tested the effects of the extracts on activities of CYP1A1 and CYP1A2, represented by ethoxyresorufin Odeethylase (EROD) and methoxyresorufin Odemethylase (MROD), respectively. Both aqueous and organic extracts inhibited EROD activity at all dose levels, while the inhibitory effect was only observed at high doses with regard to MROD activity. Furthermore, pre-treatment of Chinese hamster V79cells with PC extracts significantly reduced H2O2 - induced-DNA damage, indicating that PC extracts provide a protective effect against oxidative DNA damage. These results indicate that whole-mushroom extracts contain compounds that may inhibit the metabolic activation of B[a]P by CYP1A1 as well as prevent oxidative DNA damage.
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