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Effects of Man-made Environmental Toxic Agents in Mouse Germ Cells

Research Project

Project/Area Number 05680469
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 環境影響評価(含放射線生物学)
Research InstitutionKanazawa Medical University

Principal Investigator

INOUE Masao  Kanazawa Med.University, Med.Res.Institute, Lecture, 総合医学研究所, 講師 (60064565)

Co-Investigator(Kenkyū-buntansha) KURIHARA Takayuki  Kanazawa Med.University, Med.Res.Institute, Lecture, 総合医学研究所, 講師 (20064595)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsMan-made environmental toxic agents / Mouse germ cells / Dioxin (TCDD) / DNA damages / DNA repair / Transgenerational effects / 精子DNA切断 / 染色体異常 / ダイオキシン
Research Abstract

A man-made environmental toxic agent used this experiment was 2,3,7,8- Tetrachloro dibenzo-pdioxin (TCDD) in dioxin groups. Animals used this experiment were C3H/He male mice, approximately 10 weeks old at the start of each experiment.
By an i.p.injection of TCDD,about 4% of TCDD in liver was detected in testis. This result indicates that TCDD arrived to testis is very small in quantity compared with methyl nitrosourea (MNU) which detected 68% of liver in testis. Sertoli cells were received cellular damages by an i.p.injection with 100mug/kg of TCDD.These damages increased with time after the injection and thereafter extended to germ cells. However, unscheduled DNA synthesis (UDS) , DNA strand breaks and chromosome aberrations in germ cells were not detected by an i.p.injection with 100 mug/kg of TCDD.These results suggest that above cellular damages were not caused by DNA damages in those cells. However, when mice were injected with 1 mug of TCDD into each testis (corresponds to 12.5 m … More g/kg) , UDS was detected in the germ cells of early spermatogonia to early spermatid but not in germ cells of late spermatid to spermatozoa, in the same manner as the results of i.p.treatments with genotoxic alkyl compounds or X-ray irradiation. This result suggests that the quantity of TCDD in order to detect UDS in germ cells is in need of the quantity more than 1mug in each testis. Binding activity of TCDD to sperm head was about 4 times of that of MNU,and the activity to each germ cell stage was like to that of methyl methansulfonate.
From above results, the following was suggested. In order to detect DNA damages and repair in mouse germ cells by an i.p.treatment with TCDD,the amounts of the treatment are in need of several hundreds mg/kg over the amounts as genotoxic alkyl compounds reported previously. That is, if the amount of TCDD that is possible of search of DNA damages and repair arrived in the germ cells, it is expected that TCDD gives transgenerational effects to F1 offspring by same manner as genotoxic alkyl compounds. By an i.p.treatment with 100 mug/kg of TCDD,however, cellular damages were caused in germ cells through Sertoli cells and about 30% of mice died for less than 1 month after the treatment. Therefore, TCDD,as far as an i.p.treatment to male mice, is less possibility to induce the transgenerational effects such as dominant lethals or specific locus mutations in post-implantation. Less

Report

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

Research Products

(6 results)

All Other

All Publications (6 results)

  • [Publications] Masao Inoue: "Effects of treatment with methyl methanesulfonate during meiotic and postmeiotic stages and maturation of spermatozoa in mice" Mutation Research. 294. 179-186 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 井上 雅雄: "ENU処理による雄マウス生殖細胞のDNA損傷とその修復" 変異原試験. 3. 232-237 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masao Inoue, Takayuki Kurihara, et al.: "Effects of treatment with methyl methanesulfonate during meiotic and postmeiotic stages and maturation of spermatozoa in mice" Mutation Research. 294. 179-186 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masao Inoue and Minoru Miyagoshi.: "ENU-induced DNA damages and their repair in germ cells of male mice" Japan.J.Mutagenisity Tests on Chemicals. 3. 232-237 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 井上雅雄: "ENU処理による雄マウス生殖細胞のDNA損傷とその修復" 変異原試験. 3. 232-237 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masao Inoue: "Effects of treatment with methylmethanesulfonate during meiotic and postmeiotic stages and maturation of spermatozoa in mice" Mutation Research. 294. 179-186 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-03-31   Modified: 2016-04-21  

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