Ontogenetic expression of polycyclic aromatic compound-inducible monooxygenase activities and forms of cytochrome P-450 in rabbit. Evidence for temporal control and organ specificity of two genetic regulatory systems

Journal Article · Sun Jul 10 04:00:00 EDT 1977 · J. Biol. Chem.; (United States)

OSTI ID:7323708

Atlas, S A; Boobis, A R; Felton, J S; Thorgeirsson, S S; Nebert, D W

Developmental curves of liver microsomal cytochrome P-450 total content and five monooxygenase activities from control and 3-methylcholanthrene-treated New Zealand White rabbits were determined from 5 days prior to birth to adulthood (110 days of age). Microsomes were concomitantly analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. N-Acetylarylamine (2-acetylaminofluorene) N-hydroxylase induction by 3-methylcholanthrene parallels quite closely increases in an electrophoretic band of 54,000 daltons and the approximately 2 nm spectral shift to the blue in the Soret peak of the reduced hemoprotein CO complex, and the induced N-hydroxylase activity is markedly inhibited by ..cap alpha..-naphthoflavone in vitro; these parameters develop in rabbits of age 10 days and older. Biphenyl 4-hydroxylase induction by 3-methylcholanthrene is at least 2-fold in the fetus and neonate for the first 10 days of age, is less than 2-fold between 16 and 40 days of age, and is absent in rabbits 50 days and older. Cytochrome P-450-mediated monooxygenases are implicated in the metabolic potentiation of certain carcinogens and other environmental pollutants. These data provide evidence for at least three different tissue-specific forms of regulation of inducible monooxygenase activities and their associated P-450 subunits by tissue-specific genes and the modification of these by temporal genes. These two types of genetic control may play a role in the susceptibility to chemical carcinogenesis or toxicity as a function of either age or tissue localization.

• Research Organization: National Institutes of Health, Bethesda, MD
• OSTI ID: 7323708
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 252:13; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BIOLOGICAL EFFECTS
BODY
CELL CONSTITUENTS
CYTOCHROMES
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HYDROCARBONS
LIVER
MAMMALS
METABOLISM
MICROSOMES
ONTOGENESIS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PIGMENTS
POLYCYCLIC AROMATIC HYDROCARBONS
RABBITS
VERTEBRATES