| Project/Area Number |
07554043
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
遺伝
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| Research Institution | TOKAI UNIVERSITY |
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Principal Investigator |
GONDO Yoichi TOKAI UNIVERSITY,THE INSTITUTE OF MEDICAL SCIENCES,ASSOCIATE PROFESSOR, 総合医学研究所, 助教授 (40225678)
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| Co-Investigator(Kenkyū-buntansha) |
MINOWA Osamu CANCER INSTITUTE DEPARTMENT OF CELL BIOLOGY RESEARCH ASSOCIATE, 細胞生物部, 研究員 (00181967)
NATATSU Yoshimiti OOSAKA UNIVERSITY,INSTITUTE FOR MOLECULAR AND CELLULAR BIOLOGY,ASSISTANT PROFESS, 細胞生体工学センター, 助手 (00207820)
NIWA Ootsura KYOTO UNIVERSITY RADIATION BIOLOGY CENTER PROFESSOR, 放物線生物研究センター, 教授 (80093293)
MAKI Hisaji NARA INSTITUTE OF SCIENCE AND TECHNOLOGY,GRADUATE SCHOOL OF BIOSCIENCES,PROFESSO, バイオサイエンス研究所, 教授 (20199649)
SOFUNI Toshio NATIONAL INSTITUTE OF HEALTH SCIENCES,DIVISION OF GENETICS AND MUTAGENESIS,DIREC, 変異遺伝部, 部長(研究職) (20132889)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Transgenic mouse / Mutation ; in vivo / rpsL gene / Tumorigenicity screening / Genotoxicity test / Mutagen / Mutagenicity test / Shuttle vector |
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| Research Abstract |
We have developed a transgenic system to detect somatic mutations in vivo by using the E.coli rpsL gene as a positively selectable marker. In addition to the pML4 shuttle vector, a newly constructed pSSW was also introduced into mice. As results ; 1) the background mutant frequency was reduced to 1x10^<-5>,2) the efficiency of the detection increased 3-fold, 3) methylated shuttle vectors were rescued in E.coli, 4) the mode of mutations was the indistinguishable between two shuttle systems. Mutagens, i.e., MNU,MeIQx, AOM,AFBI and Trp-P-2 were examined so far. Effects of antimutagenicity of chlorophirin and EGCG were also studied. The mutagenicity of rpsL was extensively analyzed in the E.coli system in terms of mutators of hosts and/or hot spot sequences in the rpsL gene. The comparison was made with newly developed positive selection systems with the gpt and cII transgenic mice in addition to MutaMouse and BigBlue. The delayd radiation effects were recognized in mice as well as Drosophila, which are the candidate systems for the future research. Progenies were obtained from the mating of pML4-or pSSW-transgenic mice to the mice deficient for the XPA or MLH1 gene. The mutation spectra studies suggested the possibility to distinguish the effect of mutagenicity from the effect of cytotoxicity of an administered agent.
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