Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Effects of Enzyme Inducers and Glutathione on the Embryotoxicity of Cyclophosphamide in Cultured Rat Embryos

효소유도제 및 glutathione이 전배자배양된 랫드태자에서 cyclophosphamide의 독성에 미치는 영향

  • 한순영 (국립보건안전연구원 독성부) ;
  • 신재호 (국립보건안전연구원 독성부) ;
  • 권석철 (국립보건안전연구원 독성부) ;
  • 강명옥 (국립보건안전연구원 독성부) ;
  • 이유미 (국립보건안전연구원 독성부) ;
  • 김판기 (국립보건안전연구원 독성부) ;
  • 양미라 (단국대학교 의과대학) ;
  • 박귀례 (국립보건안전연구원 독성부) ;
  • 장성재 (국립보건안전연구원 독성부)
  • Published : 1995.06.01
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Abstract

Cyclophosphamide (CP) must be enzymatically activated by cytochrome P450(CYP)-linked mixed-function oxidation pathway to be either mutagenic or teratogenic. Influences of alterations in hepatic mixed-function oxidase acitivity and glutathione (GSH) content on the embryotoxicity of CP were studied in rat whole embryo culture system. The embryotoxicity of CP was compared using rat S-9 fraction (S-9) pretreated with chemicals inducing different CYP isozymes, acetone (ACE), Aroclor 1254 (ARO), $\beta$-naphthoflavone (NAF) and phenobarbital (PHE). When 10.5 day embryos were cultured in the immediately centrifuged rat serum for 48 hrs using general gas char{ging schedule, CP$(40{\mu}g/ml)$ with S-9 induced by either NAF or PHE increased the incidence of realformations and significantly decreased embryonic growth compared with the non-induced S-9 group. ACE or ARO induced S-9 group showed no significant difference in embryonic growth. These data suggest that PB and/or NAF inducible CYP isoenzymes are mainly involved in the activation of CP. To examine the effect of GSH on the embryotoxicity of CP, 10.5 day embryos were exposed to CP and S-9 after preincubation with 10 mM of GSH for 3 hrs. In the GSH pretreated group the growth of embryos increased significantly compared with that of the untreated group, suggesting that GSH may protect embryos in culture from some toxic effects of CP.

Keywords

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