Localization of CYP1A1 mRNA in human lung byin situ hybridization: Comparison with immunohistochemical findings

Saarikoski, Sirkku T.; Husgafvel‐Pursiainen, Kirsti; Hirvonen, Ari; Vainio, Harri; Gonzalez, Frank J.; Anttila, Sisko

doi:10.1002/(sici)1097-0215(19980703)77:1<33::aid-ijc7>3.0.co;2-0

Cited by 36 publications

(25 citation statements)

References 21 publications

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“…Among them, immunohistochemical studies revealed that CYP2S1 protein is highly expressed in both bronchi and bronchioli but is very low in the alveolar lining cells (Saarikoski et al, 2005). In contrast, the expression of CYP1A1 protein was intense in bronchiolar epithelium of peripheral lung and type II alveolar epithelial cells (Saarikoski et al, 1998). The cellular localization pattern of CYP2A13 protein in human respiratory tract is much more similar to that of CYP2S1.…”

Section: Discussionmentioning

confidence: 99%

CYP2A13 in Human Respiratory Tissues and Lung Cancers: An Immunohistochemical Study with A New Peptide-Specific Antibody

Zhu¹,

Thomas²,

Lǚ³

et al. 2006

Drug Metab Dispos

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ABSTRACT:Human cytochrome P450 2A13 (CYP2A13) is highly efficient in the metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and another potent carcinogen, aflatoxin B1 (AFB1). Although previous studies demonstrated that CYP2A13 mRNA is predominantly expressed in human respiratory tissues, expression of CYP2A13 protein in these tissues and the involved cell types have not been determined because of the lack of CYP2A13-specific antibodies. To explore the toxicological and physiological function of CYP2A13, it is important to understand the tissue/cellular distribution of CYP2A13 protein.In this study, we generated a peptide-specific antibody against human CYP2A13 and demonstrated by immunoblot analysis that this antibody does not cross-react with heterologously expressed human CYP2A6 and mouse CYP2A5 proteins, both sharing a high degree of amino acid sequence similarity with CYP2A13. Nor does the antibody cross-react with heterologously expressed human CYP3A4, CYP2S1, or any of the cytochrome P450 enzymes present in the human liver microsomes. Using this highly specific antibody for immunohistochemical staining, we detected a high level of CYP2A13 protein expression in the epithelial cells of human bronchus and trachea, but a rare distribution in the alveolar cells. There was little expression of CYP2A13 protein in different types of lung cancers. In consideration of the high efficiency of CYP2A13 in NNK metabolic activation, our result is consistent with the reported observations that most smoking-related human lung cancers are bronchogenic and supports that CYP2A13-catalyzed in situ activation may play a critical role in human lung carcinogenesis related to NNK and AFB1 exposure.

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Section: Discussionmentioning

confidence: 99%

CYP2A13 in Human Respiratory Tissues and Lung Cancers: An Immunohistochemical Study with A New Peptide-Specific Antibody

Zhu¹,

Thomas²,

Lǚ³

et al. 2006

Drug Metab Dispos

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“…These data correlate well with earlier studies on in vivo pulmonary CYP expression. CYP1A1 has been shown to be inducible by cigarette smoking and it is mainly located in the peripheral lung (7)(8)(9)13). Tobacco smoke-induced CYP1B1 mRNA has been found in bronchial cells (11) and alveolar macrophages (R. Piipari, unpublished data).…”

Section: Discussionmentioning

confidence: 98%

“…CYP proteins in type II cells include inducible CYP1A1 (9,13,31), CYP2B6 (31), CYP2E1 (31), and CYP3A (14,15,32) (Table 1). Functional epoxide hydrolase and ethoxyresorufin O-deethylase (EROD) activities have also been detected in these cells (33).…”

Section: Discussionmentioning

confidence: 99%

“…These CYP forms are expressed in various human pulmonary cell types. The main target of lung cancer caused by tobacco, the bronchial epithelial cells, expresses CYP1A1 (7)(8)(9)(10)(11)(12)(13) and CYP1B1 (10,11), and these CYP forms are inducible by cigarette smoking. In addition, airway epithelial cells contain CYP3A5 messenger RNA (mRNA) and protein (12,14,15).…”

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confidence: 99%

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Induction and Regulation of Xenobiotic-Metabolizing Cytochrome P450s in the Human A549 Lung Adenocarcinoma Cell Line

Hukkanen

Lassila

Päivärinta

et al. 2000

Am J Respir Cell Mol Biol

140

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Several cytochrome P450 (CYP) enzymes are expressed in the human lung, where they participate in metabolic inactivation and activation of numerous exogenous and endogenous compounds. In this study, the expression pattern of all known xenobiotic-metabolizing CYP genes was characterized in the human alveolar type II cell-derived A549 adenocarcinoma cell line using qualitative reverse transcriptase/polymerase chain reaction (RT-PCR). In addition, the mechanisms of induction by chemicals of members in the CYP1 and CYP3A subfamilies were assessed by quantitative RT-PCR. The expression of messenger RNAs (mRNAs) of CYPs 1A1, 1B1, 2B6, 2C, 2E1, 3A5, and 3A7 was detected in the A549 cells. The amounts of mRNAs of CYPs 1A2, 2A6, 2A7, 2A13, 2F1, 3A4, and 4B1 were below the limit of detection. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced CYP1A1 and CYP1B1 mRNAs 56-fold and 2.5-fold, respectively. CYP3A5 was induced 8-fold by dexamethasone and 11-fold by phenobarbital. CYP3A4 was not induced by any of the typical CYP3A4 inducers used. The tyrosine kinase inhibitor genistein and the protein kinase C inhibitor staurosporine blocked TCDD-elicited induction of CYP1A1, but they did not affect CYP1B1 induction. Protein phosphatase inhibitors okadaic acid and calyculin A enhanced TCDD-induction of CYP1B1 slightly, but had negligible effects on CYP1A1 induction. These results suggest that CYP1A1 and CYP1B1 are differentially regulated in human pulmonary epithelial cells and give the first indication of the induction of CYP3A5 by glucocorticoids in human lung cells. These results establish that having retained several characteristics of human lung epithelial cell CYP expression, the A549 lung cell line is a valuable model for mechanistic studies on induction of the pulmonary CYP system.

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“…It should be emphasized, however, that these tissues also possess the ability to activate PAHs to reactive intermediates. In the lung, the highest expression of CYP1A1 has been reported in the terminal bronchiolar epithelium (Mace et al 1998;Saarikoski et al 1998). Of interest also is the CYP1A1-dependent metabolic capacity of the endothelial cells (Granberg et al 2000 and references therein).…”

Section: Absorption Disposition and Metabolism Of Pahs In The Respimentioning

confidence: 99%

Cancer Risk Assessment, Indicators, and Guidelines for Polycyclic Aromatic Hydrocarbons in the Ambient Air

Boström¹,

Gerde²,

Hanberg³

et al. 2002

Environ Health Perspect

856

459

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Localization of CYP1A1 mRNA in human lung byin situ hybridization: Comparison with immunohistochemical findings

Cited by 36 publications

References 21 publications

CYP2A13 in Human Respiratory Tissues and Lung Cancers: An Immunohistochemical Study with A New Peptide-Specific Antibody

CYP2A13 in Human Respiratory Tissues and Lung Cancers: An Immunohistochemical Study with A New Peptide-Specific Antibody

Induction and Regulation of Xenobiotic-Metabolizing Cytochrome P450s in the Human A549 Lung Adenocarcinoma Cell Line

Cancer Risk Assessment, Indicators, and Guidelines for Polycyclic Aromatic Hydrocarbons in the Ambient Air

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