Teratogen-induced cell death in postimplantation mouse embryos: differential tissue sensitivity and hallmarks of apoptosis.
Teratogen-induced cell death is a common event in the pathogenesis associated with tissues destined to be malformed. Although the importance of this cell death is recognized, little information is available concerning the biochemistry of teratogen-induced cell death. We show that three teratogens, hyperthermia, cyclophosphamide and sodium arsenite induce an increase in cell death in day 9.0 mouse embryos with concurrent induction of DNA fragmentation, activation of caspase-3 and the cleavage of poly (ADP-ribose) polymerase (PARP). Teratogen-induced cell death is also selective, i. e., some cells within a tissue die while others survive. In addition, cells within some tissues die when exposed to teratogens while cells in other tissues are relatively resistant to teratogen-induced cell death. An example of the latter selectivity is seen in the cells of the developing heart, which are resistant to the cytotoxic potential of many teratogens. We show that the absence of cell death in the heart is accompanied by the complete lack of DNA fragmentation, activtion of caspase-3 and the cleavage of PARP.
Mirkes
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PE
Birth Defects Research Laboratory, Division of Congenital Defects, University of Washington, Seattle, WA 98195, USA. pemst@u.washington.edu
Little
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SA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D003520:Cyclophosphamide / Q000494:pharmacology; D053938:DNA Fragmentation; D047108:Embryonic Development / Q000502:physiology; D004789:Enzyme Activation; D005260:Female; D006257:Head / Q000196:embryology; D006321:Heart / Q000196:embryology; D006361:Heating; D051379:Mice; D009707:Nucleosomes; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011247:Pregnancy; D017670:Sodium Compounds / Q000494:pharmacology; D013194:Staining and Labeling; D013723:Teratogens / Q000494:pharmacology*
D018053:Arsenites; D009707:Nucleosomes; D017670:Sodium Compounds; D013723:Teratogens; C017947:sodium arsenite; D003520:Cyclophosphamide; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases