CYP1A2 is expressed along with CYP1A1 in the human lung

• Published in: Cancer letters Vol. 164; no. 1; pp. 25 - 32
• Main Authors: Wei, Cindy, Cacavale, Robert J., Kehoe, John J., Thomas, Paul E., Iba, Michael M.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.03.2001; Elsevier
• Subjects: 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline; Analytical, structural and metabolic biochemistry; Animals; Antibodies, Monoclonal - metabolism; Benzo(a)pyrene - metabolism; Benzo[ a]pyrene; Biological and medical sciences; Blotting, Western; CYP1A1; CYP1A2; Cytochrome P-450 CYP1A1 - biosynthesis; Cytochrome P-450 CYP1A1 - metabolism; Cytochrome P-450 CYP1A2 - biosynthesis; Cytochrome P-450 CYP1A2 - metabolism; Dose-Response Relationship, Drug; Enzymes and enzyme inhibitors; Fluorenes - metabolism; Fundamental and applied biological sciences. Psychology; Human lung; Humans; Lung - metabolism; Mice; mRNA; Mutagenicity; Mutagenicity Tests; Mutagens - metabolism; Oxidoreductases; Protein; Quinolines - metabolism; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Human lung; 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline; CYP1A2; CYP1A1; Benzo[ a]pyrene; mRNA; Mutagenicity; Protein; Surgical biopsy; Human; Enzyme; Isozyme; Gene product; Mutagenicity testing; Cytochrome P450; Lung; Gene expression; In vitro; Tissue; Ames test; Metabolic activation; Drug-metabolizing enzyme
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(00)00712-6

The expression and activity of CYP1A1 were examined in fresh, small-sized lung biopsy specimens from nine human subjects. CYP1A1 transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis of total lung RNA. CYP1A2 transcripts were detected in the RNA samples as well, and bioactivation of 2-aminofluorene (2-AF) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a CYP1A2-preferential activity, was catalyzed by the lung S 9 fractions also. Two major bands were detected in the whole homogenate by western blot analysis using CD3, a mouse anti rat CYP1A1 monoclonal that cross-reacts with rat CYP1A2 as well as with human CYP1A1 and CYP1A2. S 9 fractions from the tissues catalyzed the bioactivation of benzo[ a]pyrene (B[ a]P), a CYP1A1-preferential activity, to mutagens in the Ames assay. Our findings are in agreement with the known presence of CYP1A1 in the human lung, and provide strong evidence for the expression of catalytically functional CYP1A2 in the tissue.