PMID- 12087061 OWN - NLM STAT- MEDLINE DCOM- 20020723 LR - 20131121 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 16 IP - 9 DP - 2002 Jul TI - Embryonic prostaglandin H synthase-2 (PHS-2) expression and benzo[a]pyrene teratogenicity in PHS-2 knockout mice. PG - 1001-9 AB - 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. FAU - Parman, Toufan AU - Parman T AD - Faculty of Pharmacy and, Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 2S2. FAU - Wells, Peter G AU - Wells PG LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Isoenzymes) RN - 0 (Teratogens) RN - 3417WMA06D (Benzo(a)pyrene) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases) SB - IM MH - Abnormalities, Drug-Induced/enzymology/metabolism/mortality MH - Animals MH - Benzo(a)pyrene/pharmacokinetics/*toxicity MH - Biotransformation MH - Cyclooxygenase 2 MH - Embryo, Mammalian/*enzymology MH - Embryonic and Fetal Development/drug effects MH - Female MH - Genotype MH - Isoenzymes/*genetics/*metabolism MH - Mice MH - Mice, Knockout MH - Morphogenesis MH - Pregnancy MH - Prostaglandin-Endoperoxide Synthases/*genetics/*metabolism MH - Species Specificity MH - Teratogens/pharmacokinetics/*toxicity EDAT- 2002/06/28 10:00 MHDA- 2002/07/24 10:01 CRDT- 2002/06/28 10:00 PHST- 2002/06/28 10:00 [pubmed] PHST- 2002/07/24 10:01 [medline] PHST- 2002/06/28 10:00 [entrez] AID - 16/9/1001 [pii] AID - 10.1096/fj.01-0140com [doi] PST - ppublish SO - FASEB J. 2002 Jul;16(9):1001-9. doi: 10.1096/fj.01-0140com.