Cited by 247Pharmacogenetics and Drug MetabolismToxic Organic Pollutants ImpactMetal-Catalyzed Oxygenation Mechanisms

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Genetic expression of aryl hydrocarbon hydroxylase activity in the mouse

Nebert, Daniel W., Robinson, Joseph R., Niwa, Akira, Kumari, Kenji, Poland, Alan P.·1975·Journal of Cellular Physiology

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Abstract

Monooxygenases require NADPH and molecular oxygen during the metabolism of numerous endogenous hydrophobic substrates and carcinogenic and toxic exogenous chemicals. The complexity of these membrane-bound multicomponent drug-metabolizing enzyme systems is reviewed. What "aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity" actually represents is reviewed and discussed. At least two forms of the hydroxylase activity exist and we suggest that they are associated with different molecular species of membrane-bound CO-binding hemoprotein (i.e., they are associated with different enzyme active-sties). At least two, and probably more than two, nonlinked loci are responsible for the genetic expression of new cytochrome P1450 formation and aryl hydrocarbon hydroxylase induction--and the stimulation of 10 other monooxygenase "activities"--in the mouse treated with certain aromatic hydrocarbons. The individual variability of hydroxylase activity in an inbred and in a random-bred strain of micr is illustrated. The basal hydroxylase activity appears to be inherited differently from the aromatic hydrocarbon-inducible hydroxylase activity. The potent inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin can stimulate increases in these hepatic monooxygenase activities and p1450 formation in so-called "nonresponsive" mice, whereas inducers such as beta-naphthoflavone and 3-methylcholanthrene cannot. Thus, the genetically "nonresponsive" micr apparently possess the structural and regulatory genes ne…

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Authors: Nebert, D. W., Robinson, J. R., Niwa, A., Kumari, K., & Poland, A. P.
Affiliations: National Institutes of Health (US)
University of Rochester Medicine (US)
ORCID: Robinson, Joseph R.
Venue: Journal of Cellular Physiology
Publisher: Wiley
Published: 1975-04
Volume: 85
Issue: S1
Pages: 393-414
ISSN: 0021-9541 (ISSN-L)
1097-4652
DOI: 10.1002/jcp.1040850407
OpenAlex: W1982386536
Cited by: 247
References: 56
Citations by year: 2025: 1 · 2023: 4 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 1 · 2013: 1 · 2012: 2
FWCI: 5.75
Type: journal article
Language: en
Open access: closed
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 14763 d)
Locations: Journal of Cellular Physiology (publishedVersion)
PubMed (publishedVersion)
The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
Keywords: aryl hydrocarbon hydroxylase, mixed function oxidase, benzo[a]pyrene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, genetic polymorphism, inbred mouse strains, hepatic drug metabolism, beta-naphthoflavone, 3-methylcholanthrene
MeSH terms: Polychlorinated Dibenzodioxins, Animals, Aryl Hydrocarbon Hydroxylases, Benzopyrenes, Crosses, Genetic, Cytochrome P-450 Enzyme System, Enzyme Induction, Enzyme Inhibitors, Genes, Genes, Regulator, Hydroxylation, Liver, Mice, Inbred Strains, Microsomes, Liver, Mitomycins, Models, Biological, Multienzyme Complexes, Oxygenases, Receptors, Drug, Mice

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Genetic expression of aryl hydrocarbon hydroxylase activity in the mouse

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