Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells

• Published in: Carcinogenesis (New York) Vol. 18; no. 4; pp. 795 - 799
• Main Authors: Kelley, D J, Mestre, J R, Subbaramaiah, K, Sacks, P G, Schantz, S P, Tanabe, T, Inoue, H, Ramonetti, J T, Dannenberg, A J
• Format: Journal Article
• Language: English
• Published: England 01-04-1997
• Subjects: Benzo(a)pyrene - pharmacology; Cells, Cultured; Cyclooxygenase 2; Dinoprostone - biosynthesis; Enzyme Induction; Gene Expression Regulation, Enzymologic - drug effects; Humans; Isoenzymes - biosynthesis; Isoenzymes - genetics; Membrane Proteins; Mouth Mucosa - cytology; Mouth Mucosa - drug effects; Mouth Mucosa - enzymology; Prostaglandin-Endoperoxide Synthases - biosynthesis; Prostaglandin-Endoperoxide Synthases - genetics
• ISSN: 0143-3334
• DOI: 10.1093/carcin/18.4.795

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.