| Records |
| Author |
Wells, P.G.; Bhuller, Y.; Chen, C.S.; Jeng, W.; Kasapinovic, S.; Kennedy, J.C.; Kim, P.M.; Laposa, R.R.; McCallum, G.P.; Nicol, C.J.; Parman, T.; Wiley, M.J.; Wong, A.W. |
| Title |
Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species |
Type |
Journal Article |
| Year |
2005 |
Publication |
Toxicology and applied pharmacology |
Abbreviated Journal |
Toxicol Appl Pharmacol |
| Volume |
207 |
Issue |
2 Suppl |
Pages |
354-366 |
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| Abstract |
Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction. This minireview focuses upon several model drugs (phenytoin, thalidomide, methamphetamine), environmental chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in vivo and in embryo culture using mouse, rat and rabbit models. Embryonic prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics to free radical intermediates that initiate ROS formation, resulting in oxidation of proteins, lipids and DNA. Oxidative DNA damage and embryopathies are reduced in PHS knockout mice, and in mice treated with PHS inhibitors, antioxidative enzymes, antioxidants and free radical trapping agents. Thalidomide causes embryonic DNA oxidation in susceptible (rabbit) but not resistant (mouse) species. Embryopathies are increased in mutant mice deficient in the antioxidative enzyme glucose-6-phosphate dehydrogenase (G6PD), or by glutathione (GSH) depletion, or inhibition of GSH peroxidase or GSH reductase. Inducible nitric oxide synthase knockout mice are partially protected. Inhibition of Ras or NF-kB pathways reduces embryopathies, implicating ROS-mediated signal transduction. Atm and p53 knockout mice deficient in DNA damage response/repair are more susceptible to xenobiotic or radiation embryopathies, suggesting a teratological role for DNA damage, consistent with enhanced susceptibility to methamphetamine in ogg1 knockout mice with deficient repair of oxidative DNA damage. Even endogenous embryonic oxidative stress carries a risk, since untreated G6PD- or ATM-deficient mice have increased embryopathies. Thus, embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk. |
| Address |
Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada |
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English |
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0041-008X |
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PMID:16081118 |
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no |
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refbase @ user @ |
Serial |
68 |
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| Author |
Eisenmann V, G.D.C. |
| Title |
Caractères distinctifs des premières phalanges antérieures et postérieures chez certains équidés actuels et fossiles |
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Journal Article |
| Year |
1974 |
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Abbreviated Journal |
Bull Soc g?ol France |
| Volume |
16 |
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Pages |
352-361 |
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from Professor Hans Klingels Equine Reference List |
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1059 |
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| Author |
Eisenmann V, G.D.C. |
| Title |
Caractères distinctifs entre vrais zèbres et zèbres de Chapman d`après l`étude de 60 têtes osseuses. |
Type |
Journal Article |
| Year |
1974 |
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Abbreviated Journal |
Mammalia |
| Volume |
38 |
Issue |
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Pages |
509-543 |
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from Professor Hans Klingels Equine Reference List |
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1060 |
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| Author |
Eisenmann V, G.C. |
| Title |
Morphologie fonctionelle et environnement chez les périssodactyles. |
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Journal Article |
| Year |
1984 |
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Abbreviated Journal |
Geobios, Mém sp |
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8 |
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69 |
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from Professor Hans Klingels Equine Reference List |
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no |
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1061 |
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| Author |
Fagen Rm, G.T. |
| Title |
Play behavior and exercise in young ponies |
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Journal Article |
| Year |
1977 |
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Abbreviated Journal |
Behav Ecol Sociobiol |
| Volume |
2 |
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Pages |
267-269 |
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from Professor Hans Klingels Equine Reference List |
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no |
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1077 |
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| Author |
Green Nf, G.H. |
| Title |
The wild horse population.... |
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Journal Article |
| Year |
1977 |
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Proc National Wild Horse Forum |
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1 |
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59-65 |
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from Professor Hans Klingels Equine Reference List |
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no |
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1125 |
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| Author |
Grzimek M, G.B. |
| Title |
A study of the game of the Serengeti plains |
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Journal Article |
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1960 |
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Z Säugetierk |
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25 |
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from Professor Hans Klingels Equine Reference List |
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no |
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Serial |
1152 |
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| Author |
Penzhorn Bl, G.R. |
| Title |
Incisor wear in free – ranging Cape mountain zebras |
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Journal Article |
| Year |
1987 |
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Abbreviated Journal |
S Afr J Wildl Res |
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17 |
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99-102 |
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from Professor Hans Klingels Equine Reference List |
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no |
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Serial |
1461 |
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| Author |
Wells Sm, G.-R. |
| Title |
Social behaviour and relationship in a herd of Carmargue horses |
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Journal Article |
| Year |
1979 |
Publication |
Zeitschrift für Tierpsychologie |
Abbreviated Journal |
Z. Tierpsychol. |
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49 |
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363-380 |
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from Professor Hans Klingels Equine Reference List |
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no |
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Serial |
1700 |
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| Author |
White, D.J.; Galef Jr, B.G. |
| Title |
Mate choice copying and conspecific cueing in Japanese quail,Coturnix coturnix japonica |
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Journal Article |
| Year |
1999 |
Publication |
Animal Behaviour. |
Abbreviated Journal |
Anim. Behav. |
| Volume |
57 |
Issue |
2 |
Pages |
465-473 |
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no |
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1811 |
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