Binding of aflatoxin B1 to DNA inhibited by ajoene and diallyl sulfide.
Components of garlic have been shown to inhibit a variety of tumors induced by chemical carcinogens. In this study we determined the effects of ajoene and diallyl sulfide (DAS), two organosulfur compounds of garlic, on the metabolism and DNA binding of aflatoxin B1 (AFB1) using rat liver 9000Xg supernatant as the metabolic activation system. Organosoluble and water-soluble metabolites of [3H]AFB1 were isolated by reverse-phase high performance liquid chromatography (HPLC). The effects of ajoene and DAS on glutathione-S-transferase (GST) were determined using 1-chloro-2,4-dinitrobenzene as the substrate. Ajoene and DAS at 100 mg/ml inhibited [3H]AFB1 binding to calf thymus DNA and adduct formation. They decreased the formation of both organosoluble and water-soluble metabolites of [3H]AFB1. Neither compound significantly affected GST activity. These results indicate that ajoene and DAS affected AFB1 metabolism and DNA binding by inhibiting phase I enzymes and may therefore be considered as potential cancer chemopreventive agents.
Tadi
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Department of Natural Science, Graduate School, Loma Linda University, California 92350.
Lau
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Teel
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Herrmann
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D016604:Aflatoxin B1 / Q000378:metabolism*; D000498:Allyl Compounds; D000818:Animals; D004247:DNA / Q000378:metabolism*; D004220:Disulfides / Q000494:pharmacology*; D005737:Garlic; D005978:Glutathione / Q000378:metabolism; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D011919:Rats, Inbred Strains; D013440:Sulfides / Q000494:pharmacology*; D013454:Sulfoxides
D000498:Allyl Compounds; D004220:Disulfides; D010936:Plant Extracts; D013440:Sulfides; D013454:Sulfoxides; C038491:allyl sulfide; D004247:DNA; C048980:ajoene; D016604:Aflatoxin B1; D005978:Glutathione