Journal Article

Tobacco smoke induces CYP1B1 in the aerodigestive tract

Jeffrey L. Port, Kentaro Yamaguchi, Baoheng Du, Mariana De Lorenzo, Mindy Chang, Paul M. Heerdt, Levy Kopelovich, Craig B. Marcus, Nasser K. Altorki, Kotha Subbaramaiah and Andrew J. Dannenberg

in Carcinogenesis

Volume 25, issue 11, pages 2275-2281
Published in print November 2004 | ISSN: 0143-3334
Published online November 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh243
Tobacco smoke induces CYP1B1 in the aerodigestive tract

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Several members of the P450 family, including cytochrome P450 1B1 (CYP1B1), can convert tobacco smoke (TS) procarcinogens, including benzo[a]pyrene (B[a]P), to carcinogenic intermediates. In this study we investigated the effects of TS condensate and B[a]P on the expression of CYP1B1 in vitro and in vivo. CYP1B1 mRNA and protein were induced by both TS condensate and B[a]P in cell lines derived from the human aerodigestive tract. Treatment with TS condensate stimulated binding of the aryl hydrocarbon receptor (AhR) to an oligonucleotide containing a canonical xenobiotic response element (XRE) site and induced XRE–luciferase activity. These findings are consistent with prior evidence that polycyclic aromatic hydrocarbons, known ligands of the AhR, stimulate CYP1B1 transcription by an XRE-dependent mechanism. To determine whether these in vitro findings applied in vivo, both murine and human studies were carried out. Short-term exposure to TS induced CYP1B1 in the tongue, esophagus, lung and colon of experimental mice. In contrast, CYP1B1 was not induced by TS in the aorta of these mice. Levels of CYP1B1 mRNA were also elevated in the bronchial mucosa of human tobacco smokers versus never smokers (P < 0.05). Taken together, these results support a role for CYP1B1 in TS-induced carcinogenesis in the aerodigestive tract.

Keywords: AhR, aryl hydrocarbon receptor; B[a]P, benzo[a]pyrene; CYP1B1, cytochrome P450 1B1; DMEM, Dulbecco's modified Eagle's medium; PAHs, polycyclic aromatic hydrocarbons; SSPE, sodium chloride, sodium phosphate, EDTA buffer; TS, tobacco smoke; XRE, xenobiotic response element

Journal Article.  4503 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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