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.
Roe
A L
AL
Division of Genetic Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Snawder
J E
JE
Benson
R W
RW
Roberts
D W
DW
Casciano
D A
DA
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