HepG2 cells: an in vitro model for P450-dependent metabolism of acetaminophen.
The human hepatoma cell line, HepG2, retains many cellular functions often lost by cells in culture. This research examined the constitutive bioactivation of acetaminophen and P450-dependent activity in microsomes from HepG2 cells and the effect of 0.1% acetone pretreatment on these activities. Low levels of acetaminophen bioactivation, P450 IIE1 activity, and P450 IA1-IA2 activity were demonstrated in non-induced HepG2 microsomes. Acetone increased acetaminophen bioactivation and IIE1-dependent metabolism but not P450 IA1-IA2-dependent activity. Thus, HepG2 cells may provide an in vitro model for assessing human xenobiotic metabolism of acetaminophen and other drugs.
Division of Genetic Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
A L
AL
Roe
J E
JE
Snawder
R W
RW
Benson
D W
DW
Roberts
D A
DA
Casciano
D000082:Acetaminophen / Q000378:metabolism*; D000096:Acetone / Q000494:pharmacology; D001711:Biotransformation; D006528:Carcinoma, Hepatocellular; D019363:Cytochrome P-450 CYP1A1; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000096:Acetone; D000082:Acetaminophen; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D010089:Oxidoreductases, N-Demethylating