Cytochromes P450 involved with benzene metabolism in hepatic and pulmonary microsomes

Powley, Mark W.; Carlson, Gary P.

doi:10.1002/1099-0461(2000)14:6<303::aid-jbt2>3.0.co;2-8

Cited by 52 publications

(13 citation statements)

References 36 publications

(46 reference statements)

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“…This contrasted with results observed in rats where daily supplementation with pyridoxine hydrochloride (500 µg, IP) for 2 days led to a significant reduction of NDMA-demethylase activity to normal levels (Aramphongphan et al, 1994). Regulation of CYP2E1 by the liver as well as by extra-hepatic organs (Powley and Carlson, 2000) is highly complex and can take place at the transcriptional, post-transcriptional, translational, or post-translational levels (Hukkanen, 2000). CYP2E1 can be induced by a variety of environmental toxicants including benzene (Gonzalez-Jesso et al, 2003).…”

Section: Discussionmentioning

confidence: 56%

The effects of pyridoxine deficiency and supplementation on hematological profiles, lymphocyte function, and hepatic cytochrome P450 in B₆C₃F₁mice

Tangjarukij

Navasumrit

Zelikoff

et al. 2009

Journal of Immunotoxicology

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Section: Discussionmentioning

confidence: 56%

The effects of pyridoxine deficiency and supplementation on hematological profiles, lymphocyte function, and hepatic cytochrome P450 in B₆C₃F₁mice

Tangjarukij

Navasumrit

Zelikoff

et al. 2009

Journal of Immunotoxicology

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“…DISCUSSION CYP2F1 is expressed primarily in lung tissues with little or no expression in hepatic or other extrahepatic tissues (3,13,43). The expression of CYP2F1 has been implicated in the tissue-specific toxicity associated with many pulmonary toxicants including styrene, 3-methylindole, naphthalene, and benzene (6,8,44). All of these compounds are environmental and occupational toxicants found in sources such as cigarette smoke, gasoline, and industrial by-products.…”

Section: Investigation Of the Binding Specificity Of Lung Nuclear Extmentioning

confidence: 99%

Characterization of the Human Lung CYP2F1 Gene and Identification of a Novel Lung-specific Binding Motif

Carr

Wan

Hines

et al. 2003

Journal of Biological Chemistry

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The CYP2F1 gene encodes a cytochrome P450 enzyme capable of bioactivating a number of pulmonary-selective toxicants. The expression of CYP2F1 is highly tissue-selective; the highest expression is observed in the lung with little or no hepatic expression. The objective of these studies was to elucidate the mechanisms that govern the unique tissue-specific regulation of CYP2F1. Cosmid and bacterial artificial chromosome clones were screened and sequenced to identify a gene that spanned 14 kbp containing 10 exons, including an untranslated exon 1. Primer extension analysis and 5 -rapid amplification of cDNA ends were used to identify the transcription start site. Several sequences homologous to known cis-elements were identified in the 5 -upstream region of the CYP2F1 promoter. Transient transfection studies with luciferase reporter constructs demonstrated a significant functional lung cell-specific CYP2F1 promoter region (from position ؊129 to ؉115). DNase footprinting analysis of 1.6 kbp of the upstream sequence with nuclear extracts from human lung tissues revealed one strong DNA-protein complex at ؊152 to ؊182. This nuclear protein (called lung-specific factor, LSF) was present only in lung but not liver or heart tissues. Competitive electrophoretic mobility shift assays characterized a DNA consensus site, within the LSF-binding domain, that was highly similar to two E box motifs, but no known "E box" trans-factors were identified. These studies identified a novel LSF and its consensus sequence that may control tissue-specific expression of CYP2F1.

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“…Little CYP2F1 mRNA expression was detected in other tissues (Carr et al, 2003). Studies using mammalian cells containing low levels of heterologously expressed CYP2F1 suggested that CYP2F1 is active toward several pulmonary toxicants, including naphthalene, styrene, 3-methylindole, and benzene (Nakajima et al, 1994;Lanza et al, 1999;Powley and Carlson, 2000); however, heterologous expression of CYP2F1 in nonmammalian systems yielded nonfunctional P450 proteins (e.g., Baldwin et al, 2005). Therefore, CYP2F1-transgenic mice would be useful for studying the function of CYP2F1 in chemically induced lung toxicity.…”

Section: Introductionmentioning

confidence: 99%

Generation and Characterization of aCYP2A13/2B6/2F1-Transgenic Mouse Model

Wei

Lei

et al. 2012

Drug Metab Dispos

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ABSTRACT:CYP2A13, CYP2B6, and CYP2F1, which are encoded by neighboring cytochrome P450 genes on human chromosome 19, are active in the metabolic activation of many drugs, respiratory toxicants, and chemical carcinogens. To facilitate studies on the regulation and function of these human genes, we have generated a CYP2A13/2B6/2F1-transgenic (TG) mouse model (all *1 alleles). Homozygous transgenic mice are normal with respect to gross morphological features, development, and fertility. The tissue distribution of transgenic mRNA expression agreed well with the known respiratory tract-selective expression of CYP2A13 and CYP2F1 and hepatic expression of CYP2B6 in humans. CYP2A13 protein was detected through immunoblot analyses in the nasal mucosa (NM) (ϳ100 pmol/mg of microsomal protein; similar to the level of mouse CYP2A5) and the lung (ϳ0.2 pmol/mg of microsomal protein) but not in the liver of the TG mice. CYP2F1 protein, which could not be separated from mouse CYP2F2 in immunoblot analyses, was readily detected in the NM and lung but not the liver of TG/Cyp2f2-null mice, at levels 10-and 40-fold, respectively, lower than that of mouse CYP2F2 in the TG mice. CYP2B6 protein was detected in the liver (ϳ0.2 pmol/mg of microsomal protein) but not the NM or lung (with a detection limit of 0.04 pmol/mg of microsomal protein) of the TG mice. At least one transgenic protein (CYP2A13) seems to be active, because the NM of the TG mice had greater in vitro and in vivo activities in bioactivation of a CYP2A13 substrate, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (a lung carcinogen), than did the NM of wild-type mice.

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Cytochromes P450 involved with benzene metabolism in hepatic and pulmonary microsomes

Cited by 52 publications

References 36 publications

The effects of pyridoxine deficiency and supplementation on hematological profiles, lymphocyte function, and hepatic cytochrome P450 in B₆C₃F₁mice

The effects of pyridoxine deficiency and supplementation on hematological profiles, lymphocyte function, and hepatic cytochrome P450 in B₆C₃F₁mice

Characterization of the Human Lung CYP2F1 Gene and Identification of a Novel Lung-specific Binding Motif

Generation and Characterization of aCYP2A13/2B6/2F1-Transgenic Mouse Model

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Cytochromes P450 involved with benzene metabolism in hepatic and pulmonary microsomes

Cited by 52 publications

References 36 publications

The effects of pyridoxine deficiency and supplementation on hematological profiles, lymphocyte function, and hepatic cytochrome P450 in B6C3F1mice

The effects of pyridoxine deficiency and supplementation on hematological profiles, lymphocyte function, and hepatic cytochrome P450 in B6C3F1mice

Characterization of the Human Lung CYP2F1 Gene and Identification of a Novel Lung-specific Binding Motif

Generation and Characterization of aCYP2A13/2B6/2F1-Transgenic Mouse Model

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The effects of pyridoxine deficiency and supplementation on hematological profiles, lymphocyte function, and hepatic cytochrome P450 in B₆C₃F₁mice

The effects of pyridoxine deficiency and supplementation on hematological profiles, lymphocyte function, and hepatic cytochrome P450 in B₆C₃F₁mice