For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential

The Journal of Biological Chemistry
Nadine DraginD W Nebert

Abstract

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) induces cleft palate and hydronephrosis in mice, when exposed in utero; these effects are mediated by the aryl hydrocarbon receptor. The Cyp1a1, Cyp1a2, and Cyp1b1 genes are up-regulated by the aryl hydrocarbon receptor. To elucidate their roles in dioxin-induced teratogenesis, we compared Cyp1a1(-/-), Cyp1a2(-/-), and Cyp1b1(-/-) knock-out mice with Cyp1(+/+) wild-type mice. Dioxin was administered (25 microg/kg, gavage) on gestational day 10, and embryos were examined on gestational day 18. The incidence of cleft palate and hydronephrosis was not significantly different in fetuses from Cyp1a1(-/-), Cyp1b1(-/-), and Cyp1(+/+) wild-type mice. To fetuses carried by Cyp1a2(-/-) dams, however, this dose of dioxin was lethal; this effect was absolutely dependent on the maternal Cyp1a2 genotype and independent of the embryonic Cyp1a2 genotype. Dioxin levels were highest in adipose tissue, mammary gland, and circulating blood of Cyp1a2(-/-) mothers, compared with that in the Cyp1(+/+) mothers, who showed highest dioxin levels in liver. More dioxin reached the embryos from Cyp1a2(-/-) dams, compared with that from Cyp1(+/+) dams. Fetuses from Cyp1a2(-/-) dams exhibited a approximately 6-fol...Continue Reading

References

Jan 1, 1989·Critical Reviews in Toxicology·D W Nebert
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R R MeehanM Adesnik
Sep 15, 1987·Toxicology and Applied Pharmacology·L S BirnbaumR E Morrissey
Nov 18, 1982·Nature·A PolandE Glover
Nov 1, 1993·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·L W WeberK Rozman
Dec 1, 1995·Toxicology Letters·F J GonzalezJ M Ward
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·H C LiangD W Nebert
Mar 1, 1996·Comparative Biochemistry and Physiology. Part C, Pharmacology, Toxicology & Endocrinology·E A Hassoun, S J Stohs
Jul 18, 1997·Biochemical and Biophysical Research Communications·J J DilibertoL S Birnbaum
Jan 1, 1997·Seminars in Reproductive Endocrinology·K G Osteen, E Sierra-Rivera
Jan 14, 1998·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·J MimuraY Fujii-Kuriyama
Jun 2, 1998·The Annals of Pharmacotherapy·G D Anderson
Jan 6, 1999·Biochemical and Biophysical Research Communications·H G ShertzerT P Dalton
Feb 27, 1999·Toxicological Sciences : an Official Journal of the Society of Toxicology·J M PetersB D Abbott
May 21, 1999·Drug Metabolism Reviews·J T ButersF J Gonzalez
Jan 7, 2000·Biochemical and Biophysical Research Communications·T P DaltonD W Nebert
Jan 13, 2000·Toxicology and Applied Pharmacology·P R SinclairD W Nebert
Jun 16, 2001·Toxicological Sciences : an Official Journal of the Society of Toxicology·P L BryantB D Abbott
Mar 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nadia GormanPeter R Sinclair
Sep 6, 2002·Chemico-biological Interactions·Timothy P DaltonHoward G Shertzer
Sep 6, 2002·Chemico-biological Interactions·Patricia A HarperAllan B Okey
Oct 26, 2002·Free Radical Biology & Medicine·Albert P SenftHoward G Shertzer
Dec 14, 2002·Journal of Biochemical and Molecular Toxicology·David B Carlson, Gary H Perdew
Dec 31, 2002·Toxicology·Alvaro PugaErik S Knudsen

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Citations

Nov 28, 2006·Nature Reviews. Cancer·Daniel W Nebert, Timothy P Dalton
Dec 25, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sonya M BilliardRichard T Di Giulio
Oct 22, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Christine P CurranDaniel W Nebert
Mar 21, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Wataru YoshiokaChiharu Tohyama
Sep 1, 2012·Neurotoxicology·Christine Perdan CurranCarly Strohmaier
Jun 6, 2009·Birth Defects Research. Part A, Clinical and Molecular Teratology·Geneviève Larouche, Barbara F Hales
Jan 30, 2008·Basic & Clinical Pharmacology & Toxicology·Roger W L Godschalk, Jos C S Kleinjans
Jul 13, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Nico Scheer, C Roland Wolf
Dec 5, 2017·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Kelsey KlinefelterChristine Perdan Curran
Jul 28, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·David R BellShaun White
May 2, 2008·Epidemiology·Rolv T LieHalvard Vindenes
Apr 14, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Qiang Ma, Anthony Y H Lu
Feb 3, 2019·International Journal of Molecular Sciences·Wataru Yoshioka, Chiharu Tohyama
Nov 20, 2018·EFSA Journal·UNKNOWN EFSA Panel on Contaminants in the Food Chain (CONTAM)Laurentius Ron Hoogenboom
Oct 31, 2020·Birth Defects Research·Michael A GarlandChengji J Zhou
Jan 14, 2020·Autoimmunity Reviews·Judith MerrheimNadine Dragin

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