Expression of xenobiotic-metabolizing cytochrome P450s in human pulmonary tissues.
The purpose of the study was to obtain a comprehensive picture of the expression of cytochrome P450s (CYP) in the human lung, broncho-alveolar macrophages (BAM), and peripheral blood lymphocytes. The methods used were reverse transcriptase-polymerase chain reaction (RT-PCR) with gene-specific primers and immunohistochemistry with specific anti-peptide antibodies. In RT-PCR, CYPs 1A1, 2B6/7, 2E1, 2F1, 3A5 and 4B1 were detected in cDNA prepared from whole lung tissue. BAMs expressed CYPs 1B1, 2B6/7, 2C, 2E1, 2F1, 3A5 and 4B1. These tissues lacked CYPs 1A2, 2A6, 2D6, and 3A7. In peripheral blood lymphocytes, only CYP1B1 and CYP2E1 mRNAs were consistently detected. In immunohistochemistry with anti-CYP3A antibodies, epithelial staining of CYP3A5 was observed in 100% of individuals, while only about 20% exhibited CYP3A4 staining. CYP3A5 protein was localized in the bronchial wall, bronchial glands, bronchiolar epithelium, alveolar epithelium, vascular endothelium and alveolar macrophages. The results indicate that several different xenobiotic-metabolizing CYPs are present in the human lung, possibly contributing to in situ activation of pulmonary procarcinogens.
Raunio
H
H
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Hakkola
J
J
Hukkanen
J
J
Pelkonen
O
O
Edwards
R
R
Boobis
A
A
Anttila
S
S
D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis*; D008168:Lung / Q000201:enzymology*; D008214:Lymphocytes / Q000201:enzymology; D016676:Macrophages, Alveolar / Q000201:enzymology*; D012333:RNA, Messenger
D007527:Isoenzymes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System