title: Doxorubicin induces early embryo apoptosis by inhibiting poly(ADP ribose) polymerase.
abstract: BACKGROUND
  The effect of Doxorubicin, a widely used chemotherapeutic agent, on early mouse embryonic development has not been previously characterized.
  
  
  METHODS
  Expression of apoptosis-related genes and poly(ADP-ribose) polymerase (PARP) family genes were assessed by real-time reverse transcription polymerase chain reaction (RT-PCR). Apoptosis in mouse blastocysts was tested using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Cleaved (c)-PARP was analyzed by western blot.
  
  
  RESULTS
  A 20 h exposure to doxorubicin caused rapid cytoplasmic fragmentation, DNA condensation and disruption of the cytoskeleton in mouse embryos. Doxorubicin altered the expression of genes involved in DNA repair and apoptosis and blocked early embryonic development, suggesting that doxorubicin affects DNA synthesis and repair. Furthermore, the effect of doxorubicin on early embryo development was determined by assessing the rates of development to different stages and an apoptosis index. Both assays confirmed that doxorubicin altered embryonic development. In conclusion, doxorubicin blocked pre-implantation development in early mouse embryos by altering apoptosis-related gene expression and inactivating DNA repair by PARP.
authors.affiliation: Department of Animal Sciences, Chungbuk National University, Chungbuk, Cheongju 361-763, South Korea.
authors.forename: Qing-Ling
authors.initials: QL
authors.lastname: Wang
authors.forename: Shao-Chen
authors.initials: SC
authors.lastname: Sun
authors.forename: Jemesbond
authors.initials: J
authors.lastname: Han
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kwak
authors.forename: Nam-Hyung
authors.initials: NH
authors.lastname: Kim
authors.forename: Xiang-Shun
authors.initials: XS
authors.lastname: Cui
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology*; D046149:Embryo Culture Techniques; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015053:Zygote / Q000166:cytology / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D004317:Doxorubicin; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases