| Project/Area Number |
11680558
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | SETSUNAN UNIVERSITY |
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Principal Investigator |
NAKAMUTA Hiromichi Fac.of Pharmaceutical Sci.SETSUNAN UNIVERSITY, Instructor, 薬学部, 講師 (70164275)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA Souichi Fac.of Pharmacetical Sci.SETSUNAN UNIVERSITY, Asistant Professor, 薬学部, 助教授 (10213729)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | osteoblast / chondroblast / nodule formation / endochondral ossification / GC-MS / TCDD / estradiol / progesterone / progesterone / MC3T3-E1 cell / bone mineral content / 2,3,7,8-tetrachlorodibenzo-p-dioxin |
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| Research Abstract |
We investigated the influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on bone formation and serum sex hormone levels to exmaine the mechanism of growth retardation by exposure to dioxin in the fetus.
1. In vitro studies using osteoblastic MC3T3-E1 subclone 4 (MC4) cells revealed that TCDD (<10 nM) inhibited the formation of Ca deposits (nodule) in the extracellular matrix and alkaline phosphatase activity in dose-dependent fashion. EC5O value (≒ 1 nM) of this effect corresponded to that of CYP induction observed in hepatic cells. The inhibiting effect of dioxin on nodule formation was observed in the maturation phase of MC4 but not in mineralization phase. Dioxin had an inhibiting effect on nodule formation of chondrogenic cells ATDC5 which was an in vitro model for endochondral ossification.
2. In the organ culture of fetal mouse tibias, TCDD (10 nM) suppressed the longitudinal bone growth that was determined by the process of endochondral ossification.
3. By the administration of TCDD (25 μg/kg.p.o.), bone mineral content of tibia was decreased in rats.
4. A highly sensitive measurement for sex hormones and their metabolites was developed using ultra sensitive GC-MS.The detection limits of sex hormones were as follows : estradiol=1pg/ml, progesterone=5pg/ml and testosterone=5pg/ml. Serum levels of estradiol and progesterone increased by the treatment of low dose of TCDD (0.25 μg/kg.p.o.) and serum testosterone level also increased after the treatment of high dose of dioxin (25 μg/kg.p.o.).
These results demonstrate that dioxin prevents the proliferative process of osteogenic cells and inhibits the calcification of skeletal tissue. The exposure to TCDD in fetal period prevents the process of endochondral ossification and may cause a disturbance for bone growth.
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