| Project/Area Number |
59480421
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | National Institute of Hygienic Sciences, Biological Safety research Center |
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Principal Investigator |
OMORI Yoshihito Director of Biological Safety research Center, Natl. Inst. of Hygienic Sci., その他, 研究員 (50079307)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUHARA Morio Section Chief, Dept. of Pharmaceutical Sciences, The Institute of Public Health, 衛生薬学部, 室長 (40083745)
FUJIMORI Kannosuke Section Chief, Division of Pharmacology, Biol. Safety Res. Ctr., Natl. Inst. of, 薬理部, 室長 (60124393)
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1985: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1984: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Mixed function oxidase / Fetal liver / regenerating liver / Cytochrome P-450 / 薬物代謝酵素 |
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| Research Abstract |
Studies were done on the characterization of the mixed-function oxidases (MFO) of fetal liver to evaluate the pharmacological and toxicological potency on fetus. To elucidate the reguratory mechanism of the MFO in fetal liver, characterization of cyt.P-450-linked MFO was first done and then, the comparison of the results with those of regenerating liver which is also in active proliferation stage with reduced cyt.P-450 system was done. The activity of MFO in rat fetal liver was far lower than that of maternal or adult liver and its level increased rapidly at the end of pregnacy. In fetal liver, the level of cyt. <b_5> is relatively higher than that of cyt.P-450 and the role of cyt. <b_5> , cyt.c reductase and NADR in the synergestic effect is shown to be important. The study on the induction of MFO and the spectral and catalytic properties of induced cyt. P-450 indicated the existance of cyt.P-450 isozymes different from those of maternal and adult livers which lead us to isolate the i
… More
sozymes proper to fetal liver which is actually under study.
On the other hand, in regenerating liver of rats, a marked reduction in cyt.P-450-related MFO was observed in the first 4 days following hepatectomy. The relative level of cyt. <b_5> was slightly increased and the ratio of NADH-AHH/NADPH-AHH was increased in the first phase of regeneration. The isolation of cyt.P-450 isozymes from the regenerating livers (3 days after hepatectomy) demonstrated the existance of 3 major forms and other minor forms of cyt.P-450. Comparison with these with those isolated from normal livers using the same isolation procedures did not show any marked differences in the major forms of cyt.P-450 isozymes between the two types of livers. The present study indicated that the characteristics of MFO in fetal liver is different from those of adult, maternal or regenerating livers and that further characterization of MFO of fetal liver, especially cyt.P-450 isozymes would be important to elucidate the characteristics of drug metabolism in human fetal livers. Less
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