Tobacco smoke induces CYP1B1 in the aerodigestive tract.
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.
Department of Cardiothoracic Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA.
Jeffrey L
JL
Port
Kentaro
K
Yamaguchi
Baoheng
B
Du
Mariana
M
De Lorenzo
Mindy
M
Chang
Paul M
PM
Heerdt
Levy
L
Kopelovich
Craig B
CB
Marcus
Nasser K
NK
Altorki
Kotha
K
Subbaramaiah
Andrew J
AJ
Dannenberg
D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics*; D001564:Benzo(a)pyrene / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung; D045744:Cell Line, Tumor; D065633:Cytochrome P-450 CYP1B1; D004064:Digestive System / Q000201:enzymology*; D004790:Enzyme Induction; D006801:Humans; D008175:Lung Neoplasms; D012333:RNA, Messenger / Q000235:genetics; D012137:Respiratory System / Q000201:enzymology*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*
D012333:RNA, Messenger; D012906:Smoke; D001564:Benzo(a)pyrene; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; C585498:Cyp1b1 protein, mouse; D065633:Cytochrome P-450 CYP1B1