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Development of alternatives to animal experiments with in vitro cultures of undifferentiated embryonic cells and organ primodia

Research Project

Project/Area Number 05557002
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field General anatomy (including Histology/Embryology)
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

SHIOTA Kohei  Kyoto Univ., Fac.Med., professor, 医学部, 教授 (80109529)

Co-Investigator(Kenkyū-buntansha) TSUSHIYA Toshie  National Inst.Health, Head, 部長
ISHIBASHI Makoto  Kyoto Univ., Fac.Med., Instructor, 医学部, 助手 (30232341)
YAMAMOTO Masako  Azabu Univ., Assosiate prof., 獣医学部, 助教授 (50130901)
ARISHIMA Kazuyoshi  Azabu Univ., Assosiate prof., 獣医学部, 助教授 (10124265)
MORI Chisato  Kyoto Univ., Fac.Med., Associate Professor, 医学部, 助教授 (90174375)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1993: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsEmbryonic cell / Organ culture / In vitro culture / Developmental toxioity / Aiternatives to animal experiments / in vitro培養法 / 器官培養 / 形態形成 / マウス胎児 / ヒト胎児
Research Abstract

Effects of chemicals on cultured fetal organs
The palates of day-12.5 and day-13.5 fetal mice were explanted and exposed in vitro for 72 hr to 0.1-50 mg 5-fluorouracil (5-FU) /ml or to 5-76 mg hydroxyurea (HU) /ml. 5-FU inhibited the growth and fusion of day-12.5 palatal shelves in vitro dependently on its concentrations. Day-13.5 palates were significantly less sensitive to 5-FU than day-12.5 palates, and the minimal toxic concentrations(MTCs)of 5-FU were 0.1 and 10 mg/ml for day-12.5 and day-13.5 fetal palates, respectively. HU inhibited the in vitro growth and fusion of day-12.5 fetal palatal shelves in a concentration dependent manner, but only slightly suppressed the growth of day-13.5 fetal palates. The MTCs of HU were 19 and 76 mg/ml for day-12.5 and day-13.5 fetal palates, respectively. The palates of day-12.5 ICR fetal mice may be more suitable than day-13.5 palates for in vitro teratogen screening and for the study of mechanisms of normal and abnormal palatogenesis.
2.Usefulness of fetal organ cultures for teratogen screening
The maxillary regions of day-12.5 ICR mouse fetuses were cultured in a chemicallydefined serumless medium, and the developmental toxicity of 15 chemical teratogens on cultured palates was studied. Explanted palates were exposed in vitro for 72 hr to each drug at various concentrations. A significant in vitro toxicity was shown for ll out of the 15 compunds which are teratogenic in vivo, and the in vitro predictability for developmental toxicity was 73%. The IC_<50>(50% inhibitory concentration)values calculatrd based on palatal fusion rates appeared to be a useful index of developmental toxicty of drugs. In addition, the human risk shall be assessed by comparing the minimal toxic concentrations with maximal plasma levels in human clinical conditions.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Mino. Y, et al.: "Effects of anticonvulsant drugs on fetal mouse palates cultured in vitro" Reproductive Toxicology. 8. 225-230 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kosazuma. T, et al.: "Susceptibility of day-12.5 and day-13.5 fetal mouse palates cultured in vitro to 5-fluorouraoil and hydroyuroa" Congenital Anomalies. 34. 183-191 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takizawa. T, et al.: "Transplacetally-administered enalapril inhibits the spontaneous constriction of the ductus arteriosus in the newborn rat" Congenital Anomalies. 34. 19-23 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 塩田,浩平, 他: "胎児器官培養" 組織培養. 20. 382-385 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kosazuma. T, et al.: "In vitro developmental toxicity of aspirin and its major metabolites to cultured fetal mouse palates cultured in vitro" Congenital Anomalies. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yamamoto, Y. et al.: "Effects of metamphetamine on rat embryos cultured in vitro" Biology of the Neonates. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shiota, K: "In vitro testings in developmental toxicology." J.Kansai Assn.Exp.Anim.No.13. 37-43 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ukita, K.er al.: "Effects of prenatal alcohol exposure in mice : Influence of an ADH inhibitor and a chronic inhalation study." Reprod.Toxicol. 7. 273-281 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ukita, K.er al.: "Lack of constrictive effects of cocaine on the fetal ductus arteriosus in the rat." Cong.Anom. 33. 143-146 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takizawa, T.et al.: "Transplacentally-administered enelapril inhibits the spontaneoue constriction of the ductus arteriosus in the newborn rat." Cong.Anom. 34. 19-23 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takizawa, T.: "Inhibitory effect of enalapril on the constriction of the ductus arteriosus in newborn rats." J.Vet.Med.Sci. 56. 605-606 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mino, Y.et al.: "Effects of anticonvulsant drugs on fetal mouse palates cultured in vitro." Reprod.Toxicol. 8. 225-230 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shiota, K: "In vitro culture of embryonic organs." Tissue Culture. 20. 382-385 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kosazuma, T.et al.: "Susceptibility of day-12.5 and 13.5 fetal mouse paltes cultured in vitro to 5-fluorouracil and hydroxyurea." Cong.Anom.34. 183-191 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takizawa, T.et al.: "A calcium channel blocker verapamil inhibits the spontaneous closure of the ductus arteriosus in newborn rats." J.Toxicol.Sci. 19. 171-174 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kosazuma, T.et al.: "In vitro developmental toxicity of aspirin and its major metabolites to cultured fetal mouse palates." Cong.Anom. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yamamoto, Y.et al.: "Effects of metamphetamine on rat embryos cultured in vitro." Biol.Neonate. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mino,Y.et al.: "Effects of anticonvulsant drugs on fetal mouse palates cultured in vitro" Reproductive Toxicology. 8. 225-230 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kosazuma,T.et al.: "Susceptibility of day-12.5 and day-13.5 fetal mouse palates cultured in vitro to 5- fluorouracil and hydroyurea" Congenital Anomalies. 34. 183-191 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takizawa,T.et al.: "Transplacentally-administered enalapril inhibits the spontaneous constriction of the ductus arteriosus in the newborn rat" Congenital Anomalies. 34. 19-23 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 塩田 浩平 他: "胎児器官培養" 組織培養. 20. 382-385 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kosazuma,T.et al.: "In vitro developmental toxicity of aspirin and its major metabolites to cultured fetal mouse palates cultured in vitro" Congenital Anomalies. (印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yamamoto,Y.et al.: "Effects of metamphetamine on rat mebryos cultured in vitro" Biology of the Neonates. (印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ukita,K.,Fukui,Y.,Shiota,K.: "Effects of penatal alcohol exposure in mice" Reproductive Toxicology. 7. 273-281 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ukita,K.,Arishima,K.,Yamamoto,M.,Shiota,K.: "Lack of constrictive effects of cocaine on the fetal ductus arteriosus in the rat" Congenital Anomalies. 33. 143-146 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mino,Y.,Mizusawa,E.,Shiota,K.: "Effects of anticonvulsant drugs on fetal mouse palates cultured in vitro" Reproductive toxicology. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mori,C.,Nakamura,N.,Okamoto,Y.,Shiota,K.: "Cytochemical identification of programmed cell death in the fusing fetal mouse palate by specifice labeling of DNA fragmenatior" Anatomy and Embryology. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takizawa,T.,Arishima,K.,Yamamoto,M.,Shiota,K.: "Inhibitory effect of enalapril on the constriction of the ductus arteriosus in the rat" Journal of Veterinary Science. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 塩田 浩平: "発生毒性試験におけるin vitro試験法とその意義について" 関西実験動物学会雑誌. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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