Tobacco smoke induces CYP1B1 in the aerodigestive tract.

TitleTobacco smoke induces CYP1B1 in the aerodigestive tract.
Publication TypeJournal Article
Year of Publication2004
AuthorsPort JL, Yamaguchi K, Du B, De Lorenzo M, Chang M, Heerdt PM, Kopelovich L, Marcus CB, Altorki NK, Subbaramaiah K, Dannenberg AJ
Date Published2004 Nov
KeywordsAryl Hydrocarbon Hydroxylases, Benzo(a)pyrene, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Digestive System, Enzyme Induction, Humans, Lung Neoplasms, Respiratory System, RNA, Messenger, Smoke, Smoking

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.

Alternate JournalCarcinogenesis
PubMed ID15297370
Grant ListN01-CN-35107 / CN / NCI NIH HHS / United States
P30 ES012072 / ES / NIEHS NIH HHS / United States
R01 ES09878 / ES / NIEHS NIH HHS / United States