Suppressed mutagenicity of benzo[a]pyrene by the liver S9 fraction and microsomes from eugenol-treated rats.
The mutagenicity of benzo[a]pyrene (B[a]P) in the Ames test using liver S9 fraction prepared from rats pretreated with eugenol (4-allyl-2-methoxyphenol) was suppressed to a lower level than that obtained using liver S9 from untreated rats. There was a reverse correlation between the mutagenicity of B[a]P and the dose of eugenol administered to the animals. Similarly suppressed mutagenicity was observed when liver microsomes, instead of the S9 fraction, were used in the Ames test. The mutagenic activity of B[a]P and arylhydrocarbon hydroxylase (AHH) could not be inhibited by the direct addition of eugenol into the assay mixtures. In eugenol-treated microsomes, cytochrome P-450 content, AHH activity and total B[a]P hydroxylase activity were decreased to 81, 29 and 48% of the control values, respectively. The mutagenicity of B[a]P catalyzed by microsomes from rats fed ad libitum on a diet containing 5% eugenol in the Ames test was significantly decreased. AHH activity and total B[a]P hydroxylase activity were also decreased in these liver microsomes. These results indicate that the activation of B[a]P in rat liver by cytochrome P-450, which metabolizes B[a]P to ultimate mutagens or carcinogens, is reduced by the administration of eugenol.
D000284:Administration, Oral; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000494:pharmacology*; D001579:Benzopyrene Hydroxylase / Q000037:antagonists & inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D005054:Eugenol / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects*
D065607:Cytochrome P-450 Enzyme Inhibitors; D001564:Benzo(a)pyrene; D005054:Eugenol; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases