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Embryonic prostaglandin H synthase-2 (PHS-2) expression and benzo[a]pyrene teratogenicity in PHS-2 knockout mice¹

TOUFAN PARMAN^* and PETER G. WELLS^*,2

^* Faculty of Pharmacy and
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 2S2

²Correspondence: Peter G. Wells, Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Ontario, Canada M5S 2S2.

The developmental role of prostaglandin H synthase-2 (PHS-2), which converts xenobiotics such as benzo[a]pyrene (B[a]P) to toxic free radical intermediates, is poorly understood. In this study, we determined the embryonic expression and teratological relevance of PHS-2 in pregnant CD-1 and B6/129S7 PHS-2 knockout mice. Wild-type (+/+) B6/129S7 dams given B[a]P on gestational day (GD) 10 had three times more fetal malformations than did +/- PHS-2-deficient dams (P<0.05). GD 10–13 CD-1 embryos had high PHS-2 protein expression, and both + /+ and +/- GD 19 B6/129S7 fetuses had more B[a]P-initiated malformations and postpartum lethality than did -/- littermates (P<0.05). Thus, embryonic PHS-2 is expressed constitutively during organogenesis and contributes substantially to B[a]P teratogenicity.—Parman, T., Wells, P. G. Embryonic prostaglandin H synthase-2 (PHS-2) expression and benzo[a]pyrene teratogenicity in PHS-2 knockout mice.

Key Words: cyclooxygenase-2 • free radicals • reactive oxygen species • developmental biology • toxicology

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