HEPG2 CELLS - AN INVITRO MODEL FOR P450-DEPENDENT METABOLISM OF ACETAMINOPHEN

被引:81
作者
ROE, AL
SNAWDER, JE
BENSON, RW
ROBERTS, DW
CASCIANO, DA
机构
[1] NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079
[2] UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72206
[3] UNIV ARKANSAS MED SCI HOSP,DEPT MOLEC BIOL & BIOCHEM,LITTLE ROCK,AR 72206
关键词
D O I
10.1006/bbrc.1993.1003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 demonstrate 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. © 1993 Academic Press, Inc.
引用
收藏
页码:15 / 19
页数:5
相关论文
共 25 条
[1]   5 OF 12 FORMS OF VACCINIA VIRUS-EXPRESSED HUMAN HEPATIC CYTOCHROME-P450 METABOLICALLY ACTIVATE AFLATOXIN-B1 [J].
AOYAMA, T ;
YAMANO, S ;
GUZELIAN, PS ;
GELBOIN, HV ;
GONZALEZ, FJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (12) :4790-4793
[2]   EFFECT OF ENZYME INDUCERS ON METABOLISM OF 1-NITROPYRENE IN HUMAN HEPATOMA-CELL LINE HEPG2 [J].
BELISARIO, MA ;
ARENA, AR ;
PECCE, R ;
BORGIA, R ;
STAIANO, N ;
DELORENZO, F .
CHEMICO-BIOLOGICAL INTERACTIONS, 1991, 78 (03) :253-268
[3]   ETHOXYPHENOXAZONES, PENTOXYPHENOXAZONES, AND BENZYLOXYPHENOXAZONES AND HOMOLOGS - A SERIES OF SUBSTRATES TO DISTINGUISH BETWEEN DIFFERENT INDUCED CYTOCHROMES-P-450 [J].
BURKE, MD ;
THOMPSON, S ;
ELCOMBE, CR ;
HALPERT, J ;
HAAPARANTA, T ;
MAYER, RT .
BIOCHEMICAL PHARMACOLOGY, 1985, 34 (18) :3337-3345
[4]   INDUCTION OF DRUG-METABOLIZING ENZYMES IN HUMAN-LIVER CELL-LINE HEP-G2 [J].
DAWSON, JR ;
ADAMS, DJ ;
WOLF, CR .
FEBS LETTERS, 1985, 183 (02) :219-222
[5]  
DING X, 1990, DRUG METAB DISPOS, V8, P742
[6]   QUANTITATIVE MEASUREMENT OF CEREBRAL CYTOCHROME-P-450 BY 2ND DERIVATIVE SPECTROPHOTOMETRY [J].
GHERSIEGEA, JF ;
WALTHER, B ;
MINN, A ;
SIEST, G .
JOURNAL OF NEUROSCIENCE METHODS, 1987, 20 (03) :261-269
[7]   MIXED-FUNCTION OXIDASE AND UDP-GLUCURONYLTRANSFERASE ACTIVITIES IN THE HUMAN HEP-G2 HEPATOMA-CELL LINE [J].
GRANT, MH ;
DUTHIE, SJ ;
GRAY, AG ;
BURKE, MD .
BIOCHEMICAL PHARMACOLOGY, 1988, 37 (21) :4111-4116
[8]   ROLE OF HUMAN CYTOCHROME-P-450-IIE1 IN THE OXIDATION OF MANY LOW-MOLECULAR-WEIGHT CANCER SUSPECTS [J].
GUENGERICH, FP ;
KIM, DH ;
IWASAKI, M .
CHEMICAL RESEARCH IN TOXICOLOGY, 1991, 4 (02) :168-179
[9]   THE METABOLISM OF 1-NITROPYRENE BY HUMAN CYTOCHROMES-P450 [J].
HOWARD, PC ;
AOYAMA, T ;
BAUER, SL ;
GELBOIN, HV ;
GONZALEZ, FJ .
CARCINOGENESIS, 1990, 11 (09) :1539-1542
[10]  
JEFFERY EH, 1990, BIOL REACT INTERMED, V4, P249