Repression of cytochrome P-450 2c and its mRNA by 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), 3-methylcholanthrene (3-MC) and phenobarbital (PB) in livers from male rats

Conference · Sat Mar 01 00:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5430895

Yeowell, H N; Waxman, D J; Linko, P; Goldstein, J A

Cytochrome P-450 2c was estimated by /sup 125/I-protein A dot-blot immunoassay, androst-4-ene-3,17-dione 16..cap alpha..-OHase activity and Western blots in hepatic microsomes from the adult male rats dosed daily with 50 mg/kg 3-MC or 80 mg/kg PB at 17h (single dose) and 72h (3 doses). The mRNA for P-450 2c was quantitated by translation of polysomes in vitro. 3-MC repressed P-450 2c mRNA by 17h (65% decrease) and at 72h (44% decrease). The isozyme was repressed slightly at 17 (17%) and markedly at 72h (54%). PB produced a smaller decrease in P-450 2c mRNA (17h, 41%; 72h, 25%) and only a slight decrease in the isozyme (17h, 8%; 72h, 14%). When P-450 2c and its 16/sub ..cap alpha../-OHase activity were measured following HCB administration (50mg/kg), they were decreased by 2 days and virtually abolished by 7 days. HCB also decreased P-450 2c mRNA 30% at 2 days and 90% at 7 days. In contrast, HCB induced P-450c mRNA maximally by 17-24h (25-fold) followed by a decrease to 48% of maximal levels by 7 days. Doses of 3 and 10 mg/kg HCB decreased P-450 2c mRNA approximately 30% by 7 days. This study shows that the mRNA for a constitutive P-450 isozyme is repressed by several known inducers of P-450.

• Research Organization: NIEHS, Research Triangle Park, NC
• OSTI ID: 5430895
• Report Number(s): CONF-8604222-; TRN: 86-026826
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
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CHLORINATED AROMATIC HYDROCARBONS
BIOLOGICAL EFFECTS
CHOLANTHRENE
HYDROLASES
ENZYME ACTIVITY
PHENOBARBITAL
CYTOCHROMES
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ANESTHETICS
ANIMALS
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BETA DECAY RADIOISOTOPES
BODY
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CONDENSED AROMATICS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
HYPNOTICS AND SEDATIVES
IMMUNOASSAY
IMMUNOLOGY
INTERMEDIATE MASS NUCLEI
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ISOTOPE APPLICATIONS
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MAMMALS
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PIGMENTS
PROTEINS
PYRIMIDINES
RADIOASSAY
RADIOIMMUNOLOGY
RADIOISOTOPES
RNA
RODENTS
TRACER TECHNIQUES
VERTEBRATES
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