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Genetic expression of aryl hydrocarbon hydroxylase activity in the mouse
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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“For example, strains such as B6 display a higher affinity for ligand binding and exhibit a more robust ligand-induced response than do strains such as the DBA/2 (D2) or 129Sv (129) strains (Daniel W. Nebert et al., 1975; Poland & Glover, 1975).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Daniel W. Nebert et al., 1975
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Metadata
- 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
- 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
- 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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