Regulation of rat liver cytochrome P450j, a high affinity N-nitrosodimethylamine demethylase (NDMAD)

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

OSTI ID:6279648

Thomas, P E; Bandiera, S; Maines, S L; Ryan, D E; Levin, W

Purified IgG from sera of rabbits immunized with homogeneous P450j was absorbed to produce monospecific anti-P450j. Results using anti-P450j in ELISA show that rat liver microsomal P450j content decreases between 3 and 6 wks of age in both sexes. Several xenobiotics (Aroclor 1254, mirex and 3-methylcholanthrene) repressed P450j levels when administered to male rats. In contrast, hepatic levels of P450j were induced by isoniazid, dimethylsulfoxide, pyrazole, 4-methylpyrazole, ethanol and chemically-induced diabetes. P450j levels were measurable in kidney, whereas this isozyme was barely detectable in lung, ovaries and testes; however, extra-hepatic P450j was inducible by isoniazid. Between 80-90% of microsomal NDMAD was inhibited by anti-P450j whether the microsomes were isolated from untreated rats or animals administered inducers or repressors of P450j. Results obtained with the reconstituted system suggest that the remaining microsomal NDMAD resistant to antibody inhibition is the result of the inaccessibility of a certain proportion of P450j due to interference by NADPH-P450 reductase. P450j content and NDMAD activity correlated well in microsomes from rats of all treatment groups. The evidence indicates that P450j is the primary, and possibly only, microsomal catalyst of NDMAD at substrate concentrations relevant to hepatocarcinogenesis induced by NDMA.

• Research Organization: Roche Institute of Molecular Biology, Nutley, NJ
• OSTI ID: 6279648
• 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

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3-METHYLCHOLANTHRENE
560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BODY
CELL CONSTITUENTS
DIABETES MELLITUS
DIGESTIVE SYSTEM
DISEASES
ENDOCRINE DISEASES
ENZYME ACTIVITY
ENZYME INDUCTION
ENZYMES
GENE REGULATION
GLANDS
HYDROCARBONS
IMMUNE REACTIONS
LIVER
MAMMALS
METABOLIC DISEASES
METABOLISM
MICROSOMES
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
POLYCYCLIC AROMATIC HYDROCARBONS
RATS
RODENTS
VERTEBRATES
XENOBIOTICS