BENZO[A]PYRENE UP-REGULATES CYCLOOXYGENASE-2 GENE-EXPRESSION IN ORAL EPITHELIAL-CELLS

Cyclooxygenase may be important in the pathogenesis of smoking-related cancer because it activates carcinogens and catalyzes prostaglandin b iosynthesis. We determined the effects of benzo[a]pyrene (B[a]P), a po lycyclic aromatic hydrocarbon in tobacco smoke, on cyclooxygenase-2 (C ox-2) mRNA, protein and synthesis of prostaglandin E(2) (PGE(2)) in no rmal and transformed oral epithelial cells. Treatment with B[a]P cause d a dose-dependent increase in production of PGE(2), with a maximal in crease of similar to 100%. Enhanced synthesis of PGE(2) 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. Transien t transfections with a Cox-2 promoter construct showed that B[a]P-medi ated 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 PGE(2) or amounts of Cox-a, These data are important because B[a]P -mediated induction of Cox-2 may predispose to carcinogenesis by enhan cing the production of mutagens and the synthesis of prostaglandins.