Coumarin chemoprotection against aflatoxin B1-induced gene mutation in a mammalian cell system: A species difference in mutagen activation and protection with chick embryo and rat liver S9
✍ Scribed by Douglas E. Goeger; Karl E. Anderson; Abraham W. Hsie
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 198 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
Coumarin (1,2-benzopyrone), a natural food con-nicity with rat liver S9. When liver S9 from chick stituent, prevents polycyclic aromatic hydrocarbon-embryos pretreated with coumarin was used for aflainduced neoplasms in rats and mice, but has not toxin B 1 bioactivation, mutant frequency and cytotoxicbeen studied with other chemical carcinogens. We ity were decreased compared to liver S9 from vehicleexamined coumarin chemoprotection against afla-treated controls. Liver S9 from coumarin-treated rats toxin B 1 using the 6-thioguanine resistance mutation did not significantly affect mutant frequency or cytotoxassay in two different Chinese hamster ovary cell icity. HPLC analysis of chick embryo liver S9 incubated lines (K 1 BH 4 and AS52) with liver S9 from rats and with 1 mM aflatoxin B 1 showed a dose-dependent de-19-day-old chick embryos for aflatoxin B 1 bioactiva-crease by coumarin of aflatoxin B 1 activation to the tion. Laboratory rodents metabolize coumarin 8,9-epoxide ranging from 70% of controls at 5 mM through 3-hydroxylation, whereas 7-hydroxylation coumarin to 4% of controls at 500 mM coumarin. predominates in chick embryos and humans. Chick In contrast, coumarin produced a dose-dependent embryo liver S9 was approximately 25-fold more increase in 20 mM aflatoxin B 1 activation by rat liver effective in activating aflatoxin B 1 to the mutagenic S9, reaching twice the control levels at 500 mM and cytotoxic metabolite(s) than rat liver S9. Cou-coumarin. These findings, using a mammalian cell marin added at 50 and 500 mM with chick embryo system as a mutagenic endpoint, demonstrate liver S9 reduced the mutant frequency of 1 mM afla-marked species differences in chemoprotection by toxin B 1 by 40 and 85%, respectively. Coumarin coumarin. Environ. Mol. Mutagen. 32:64-74, up to 500 mM had no effect on aflatoxin B 1 mutage-1998 ᭧ 1998 Wiley-Liss, Inc.