Regulation of human liver cytochromes P-450 in hepatoma cells
To circumvent the difficulties inherent in human studies, they used the human hepatoma cell line, Hep G2, and specific antibody and cDNA probes to examime the regulation of HLp, a cytochrome P-450 (CP-450) inducible by glucocorticoids in human liver; HLc and HLd, human orthologs of 3-methylcholanthrene (3-MC) inducible CP-450; and HLj and HLg, additional forms of human liver CP-450. Addition to the culture medium of dexamethasone (Dex) produced dose dependent (10 -10U) increases of 3-fold for HLp protein and 8-fold for HLp mRNA measured, respectively, by quantitative immunoblotting and Northern blot analyses. HLp protein and mRNA also were increased in cultures treated with rifampicin cortivazol or phenobarbital. Induction of HLp mRNA was detectable within 2 hrs of addition of Dex, was maximal after 24 hrs, but was blocked totally when cycloheximide was added prior to Dex. These results suggest that induction of HLp by Dex is not a primary response but one that requires the production of ancillary factors through ongoing protein synthesis. In untreated cultures there was no detectable immunoreactive protein or mRNA corresponding to HLd or HLc. HLc protein and mRNA rose in cultures exposed to 3-MC (10;5-fold), B-naphthoflavone (11;4-fold), or Aroclor (17;18-fold), while HLd, HLj, and HLg proteins and mRNAs remained undetectable. They conclude that the regulation of some, but not all CP-450 genes may be studied to advantage in the Hep G2 cell line.
- Research Organization:
- Medical College of Virginia, Richmond
- OSTI ID:
- 6150349
- Report Number(s):
- CONF-870644-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA, USA, 7 Jun 1987
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
3-METHYLCHOLANTHRENE
BIOLOGICAL EFFECTS
DEXAMETHASONE
GLUCOCORTICOIDS
MIXED-FUNCTION OXIDASES
ENZYME INDUCTION
DOSE-RESPONSE RELATIONSHIPS
GENE REGULATION
HEPATOMAS
IMMUNE REACTIONS
LIVER
MAN
MESSENGER-RNA
PROTEINS
RESPONSE MODIFYING FACTORS
TUMOR CELLS
ADRENAL HORMONES
ANIMAL CELLS
ANIMALS
AROMATICS
BODY
CORTICOSTEROIDS
DIGESTIVE SYSTEM
DISEASES
ENZYMES
GLANDS
HORMONES
HYDROCARBONS
HYDROXY COMPOUNDS
KETONES
MAMMALS
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
POLYCYCLIC AROMATIC HYDROCARBONS
PREGNANES
PRIMATES
RNA
STEROID HORMONES
STEROIDS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550200 - Biochemistry