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  • Title: Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells.
    Author: Kelley DJ, Mestre JR, Subbaramaiah K, Sacks PG, Schantz SP, Tanabe T, Inoue H, Ramonetti JT, Dannenberg AJ.
    Journal: Carcinogenesis; 1997 Apr; 18(4):795-9. PubMed ID: 9111217.
    Abstract:
    Cyclooxygenase may be important in the pathogenesis of smoking-related cancer because it activates carcinogens and catalyzes prostaglandin biosynthesis. We determined the effects of benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon in tobacco smoke, on cyclooxygenase-2 (Cox-2) mRNA, protein and synthesis of prostaglandin E2 (PGE2) in normal and transformed oral epithelial cells. Treatment with B[a]P caused a dose-dependent increase in production of PGE2, with a maximal increase of approximately 100%. Enhanced synthesis of PGE2 was associated with increased amounts of Cox-2 protein. B[a]P also caused a two-fold increase in Cox-2 mRNA in both normal and transformed cells. Transient transfections with a Cox-2 promoter construct showed that B[a]P-mediated induction of Cox-2 mRNA reflected increased transcription. Levels of Cox-1 were unaffected by B[a]P. B[e]P did not affect the synthesis of PGE2 or amounts of Cox-2. These data are important because B[a]P-mediated induction of Cox-2 may predispose to carcinogenesis by enhancing the production of mutagens and the synthesis of prostaglandins.
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