Tobacco smoke induces CYP1B1 in the aerodigestive tract.

Abstract:

: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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Port JL,Yamaguchi K,Du B,De Lorenzo M,Chang M,Heerdt PM,Kopelovich L,Marcus CB,Altorki NK,Subbaramaiah K,Dannenberg AJ

doi

10.1093/carcin/bgh243

keywords:

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

2275-81

issue

11

eissn

0143-3334

issn

1460-2180

pii

bgh243

journal_volume

25

pub_type

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