Comparison of mouse and chick embryo liver and hepatoma cell lines as model systems used for enzymological estimation of toxicity potentials of organic pollutants.
Cytochromes P450-dependent monooxygenase activities were determined and compared in mouse liver microsomes and in hepatoma cell homogenates after exposure to prototype inducers of individual P450 enzymes. In vivo inductions of levels of mouse hepatic monooxygenase activities have been found as effective biochemical markers of toxicity potentials of a series of classes of xenobiotics (CYP1A induction for toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin, coplanar polychlorinated biphenyls, polycyclic aromatic hydrocarbons and related pollutants; CYP2E induction for dialkylnitrosamines and organic solvents, e.g. acetone and ethanol; CYP2B and CYP3A induction for phenobarbital- and dexamethasone-type of xenobiotics). A specific induction of CYP1A-dependent O-dealkylase activities by TCDD was found in Hepa-1 and Hep G2 cell cultures, but no in vitro induction of other P450 enzymes was found after the treatment with phenobarbital, acetone or dexamethasone. Therefore, mouse liver is a suitable in vivo system for the testing of inducing effects of xenobiotics on all relevant P450 forms, while hepatoma cell cultures are usable only for the bioassay of TCDD-like toxicity.
Machala
M
M
Veterinary Research Institute, Brno, Czech Republic.
Mátlová
L
L
Nezveda
K
K
Turánek
J
J
Horavová
P
P
Granátová
M
M
Nevoránková
Z
Z
D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004785:Environmental Pollutants / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018675:Toxicity Tests / Q000379:methods*; D014407:Tumor Cells, Cultured
D004785:Environmental Pollutants; D003577:Cytochrome P-450 Enzyme System