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.
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 (Ah) 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 O-deethylase (EROD) and methoxyresorufin O-demethylase (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.
El Bohi
Khlood M
KM
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University.
Sabik
Laila
L
Muzandu
Kaampwe
K
Shaban
Zein
Z
Soliman
Mohamed
M
Ishizuka
Mayumi
M
Kazusaka
Akio
A
Fujita
Shoichi
S
D000818:Animals; D016587:Antimutagenic Agents; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000633:toxicity; D001688:Biological Products / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors; D009152:Mutagenicity Tests; D020076:Pleurotus; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*
D016587:Antimutagenic Agents; D001688:Biological Products; D001564:Benzo(a)pyrene; D006861:Hydrogen Peroxide