Regulation of cytochrome P-450j in rat hepatocytes in vivo and in primry monolayer culture

Conference · Fri May 01 04:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6279596

Hunt, C M; Molowa, D T; Thomas, P E; Levin, W; Guzelian, P S; Wrighton, S A

Cytochrome P-450j is of importance because it metabolically activates carcinogens and cytotoxic agents. They treated groups of 4 rats with 10% ethanol (EtOH) or 0.1% isoniazid (INH) and found that the amount of liver microsomal P-450j protein was increased 1.5- and 2.4 fold, respectively, over untreated control levels. When liver RNA samples were subjected to Northern and slot blot analyses, a 1.8 kb RNA species that hybridized with a cDNA probe which encodes for HLj (the human ortholog of P-450j) was increased 1.6- and 1.7-fold, respectively, in EtOH- and INH-treated rats as compared to controls. To investigate the P-450j induction mechanism, they isolated hepatocytes from untreated rats and found that when the cells were incubated on an extracellular biomatrix in serum free medium, the amount of P-450j immunoreactive protein decrease to < 50% of the level at time 0 after 72 h in culture and < 25% after 120h. Additions to the culture medium of pyrazole, hydrazine, or INH for 72 h increased P-450j immunoreactive protein up to 4.5-fold, 2.4-fold, and 1.6-fold, respectively, over control values. Moreover, P-450j mRNA decreased becoming undetectable within 24-48 h in culture. Additions of pyrazole but not other inducers increased P-450j mRNA to detectable levels. They conclude that at least some inducers of P-450j act directly on the hepatocyte by a mechanism(s) that involves both increases in P-450j mRNA and, apparently, other post-transcriptional events.

• Research Organization: Medical College of Virginia, Richmond
• OSTI ID: 6279596
• Report Number(s): CONF-870644-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560300* -- Chemicals Metabolism &amp; Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIMICROBIAL AGENTS
AZOLES
BIOLOGICAL EFFECTS
DRUGS
ENZYME INDUCTION
ENZYMES
ETHANOL
GENE REGULATION
HETEROCYCLIC COMPOUNDS
HYDRAZIDES
HYDRAZINE
HYDROXY COMPOUNDS
IMMUNE REACTIONS
IN VIVO
ISONIAZID
LIVER CELLS
MAMMALS
MESSENGER-RNA
MIXED-FUNCTION OXIDASES
NITROGEN COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
PYRAZOLES
RATS
RESPONSE MODIFYING FACTORS
RNA
RODENTS
SOMATIC CELLS
TOXICITY
VERTEBRATES