Inhibition of metabolic activation of the promutagens, benzo[a]pyrene, 2-aminofluorene and 2-aminoanthracene by furanochromones in Salmonella typhimurium.
Khellin, a naturally occurring furanochromone (Ammi visnaga fruits), inhibited the mutagenicity of the promutagens benzo[a]pyrene, 2-aminofluorene and 2-aminoanthracene in Salmonella typhimurium TA98. The effect varied greatly and depended on the S9 fraction used. Cytosolic activation of 2-aminoanthracene was also inhibited. Khellin produced no effect or only weak activity against the direct acting mutagens 2-nitrofluorene, 4-nitro-o-phenylenediamine, 1-nitropyrene and ethylmethane sulfonate (in TA100). Daunomycin mutagenicity was inhibited to a greater extent. Visnagin was more toxic, but showed similar effects. Khellol and its glucoside were inactive against all the mutagens tested. We conclude that khellin acts as an inhibitor or the microsomal cytochrome P450 sub-enzymes analogous to the related furanocoumarins and is also capable of inhibiting cytosolic enzymes. The extract from Ammi visnaga fruits showed a higher inhibition potency than khellin alone against 2-aminoanthracene, 1-nitropyrene and daunomycin. This might be due to additional inhibitors, e.g. coumarins, or to the synergistic effects of accompanying compounds.
Schimmer
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Institut für Botanik und Pharmazeutische Biologie, Universität Erlangen-Nürnberg, Germany.
Rauch
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D000818:Animals; D000873:Anthracenes / Q000378:metabolism / Q000633:toxicity; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity; D002839:Chromans / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005449:Fluorenes / Q000378:metabolism / Q000633:toxicity; D005638:Fruit / Q000737:chemistry; D007666:Khellin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity*; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects*; D019324:beta-Naphthoflavone / Q000494:pharmacology
D000873:Anthracenes; D016587:Antimutagenic Agents; D002839:Chromans; D005449:Fluorenes; D009153:Mutagens; D010936:Plant Extracts; D001564:Benzo(a)pyrene; C012177:2-aminofluorene; D007666:Khellin; D019324:beta-Naphthoflavone; C006593:2-anthramine; D003577:Cytochrome P-450 Enzyme System; C044999:visnagin; D003630:Daunorubicin