Bioassay for determining 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEs) in human hepatoma Hepg2 cells.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), and benz[a]anthracene (BA) highly induce cytochrome P4501A1, determined by aryl hydrocarbon hydroxylase (AHH) activity, in human hepatoma HepG2 cells within 24 h. AHH activity induced by TCDD and TCDF persists for at least 48 h. In contrast, AHH activity induced by BA rapidly declines, although the amounts applied are 4-5 orders of magnitude higher than those of TCDD or TCDF. AHH induction in HepG2 cells differs from that in rat hepatoma cells H4IIEC3/T in two aspects: (1) HepG2 cells are 20 times less sensitive to the test compounds than H4IIEC3/T cells. (2) TCDF-induced AHH activity does not persist in the rat cells. The results suggest that human HepG2 cells, because of their low sensitivity, are inferior to rat H4IIEC3/T cells for determining TCDD equivalents in environmental samples. They may be useful for investigating species dependent differences in the toxicokinetics of individual polyhalogenated aromatic hydrocarbon congeners.
Wiebel
F J
FJ
Institut für Toxikologie, GSF-Forschungszentrum für Umwelt und Gesundheit, Neuherberg/München, FRG.
Wegenke
M
M
Kiefer
F
F
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects / Q000378:metabolism; D001551:Benz(a)Anthracenes / Q000493:pharmacokinetics; D001572:Benzofurans / Q000493:pharmacokinetics*; D001681:Biological Assay / Q000379:methods*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004785:Environmental Pollutants / Q000493:pharmacokinetics*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology*; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics*; D051381:Rats; D014407:Tumor Cells, Cultured
D001551:Benz(a)Anthracenes; D001572:Benzofurans; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; C030935:benz(a)anthracene; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C014211:2,3,7,8-tetrachlorodibenzofuran