Mutagenic activation and detoxification of benzo[a]pyrene in vitro by hepatic cytochrome P450 1A1 and phase II enzymes in three meat-producing animals.
The mutagenic activation activity of hepatic microsomes from three meat-producing animals (cattle, deer and horses) was compared with those of rats as a reference species. In the Ames Salmonella typhimurium TA98 assay, the liver microsomes of all examined animals mutagenically activated benzo[a]pyrene, an ideal promutagens, in terms of production of histidine-independent revertant colonies. The microsomes of horses had the highest ability to produce revertant colonies of the examined animals under both low and high substrate concentrations. Inhibition of this mutagenic activity using alpha-naphthoflavone, anti-rat CYP1A1, CYP3A2 and CYP2E1 antibodies suggests that this activity was mainly because of CYP1A1 in these animals as well as in rats. The addition of co-factors for two phase II enzymes, microsomal UDP glucoronosyl transferase and cytosolic glutathione-S-transferase, reduced the production of the revertant colonies in a concentration-dependent manner. Interestingly, horses had the highest reduction rate among the examined animals, suggesting that phase II enzymes play a great role in producing a state of balance between the bioactivation and detoxification of xenobiotics in these meat-producing animals. This report is the first to investigate the mutagenic activation activity of the hepatic microsomes and the role of phase II enzymes against this activity in meat-producing animals.
Darwish
W
W
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo 060-0818, Japan.
Ikenaka
Y
Y
Eldaly
E
E
Ishizuka
M
M
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000737:chemistry / Q000633:toxicity*; D001711:Biotransformation; D002417:Cattle; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003670:Deer / Q000502:physiology*; D014453:Glucuronosyltransferase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006736:Horses / Q000502:physiology*; D008658:Inactivation, Metabolic; D007202:Indicators and Reagents; D008099:Liver / Q000201:enzymology*; D008460:Meat; D008565:Membrane Proteins / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology; D009152:Mutagenicity Tests; D051381:Rats
D007202:Indicators and Reagents; D008565:Membrane Proteins; D001564:Benzo(a)pyrene; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C465260:Cyp3a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D014453:Glucuronosyltransferase; D005978:Glutathione