HEALTH RISK ASSESSMENT OF ENDOCRINE DISRUPTERS BASED ON DEVELOPMENT, ARCHITECUTURE AND PHYSIOLOGICAL FUNCTION IN THE LUNG.

基于肺部发育、结构和生理功能的内分泌干扰物的健康风险评估。

• 批准号: 11480144
• 负责人: KAGAWA Jun
• 金额: $ 9.15万
• 依托单位: TOKYO WOMEN'S MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11480144/
• 关键词: ENDOCRINE DISRUPTERS; LUNG DEVELOPMENT AND ARCHITECUTURE; HEALTH RISK ASSESSMENT; BONE METABOLISUM; DEVELOPMENT OF FETUS BONE; FETUS OSSIFICATION; SCREENING TEST; PULMONARY FUNCTION; 肺の発生; 胎仔骨; 合成女性ホルモン; 内分泌撹乱化学物貭; 3-メチルコラントレン; ジュチルベスタノール; ア

Development of an appropriative health assessment for endocrine disrupters (EDCs) was studied based on development, architecture, and physiological functions of the lung.1. BALB/c female mice born to dame treated with diethyistilbestrol (DES) demonstrated significant increase of body weight gain with six different strains of mice.2. Female babies born to dame treated with DES showed increases of thymus weight and percentage of B-cells in spleen compared with those of the control group of BALB/c. 3. Expressions of CYP2F2 derived from Clara cells, P450 reductase, collagen III and IV mRNAs in the lung were reduced in 10-days-old babies born from dam treated with DES compared with non-treated mice. 4. Pathological changes in cardiopulmonary tissues of babies born to six strains of dame treated with DES were not significantly different from those of corresponding control groups. 5. The effects of 3- methylcholanthrene (3MC) on the metabolism of bone were examined using in vitro culture syst … More em. 3MC decreased differentiation and proliferation of osteoblasts and osteoclasts. Results suggested that 3MC might exert critical effects on bone metabolism.6. The effects of EDCs on formation of bone were studied in mouse fetuses. Abnormalities of bone morphology and delay in ossification were shown in mouse fetuses treated with EDCs. Delayed ossification was seen in the cervical and thoracic vertebrae and limbs. In the limbs, delayed ossification was observed in the metacarpals and/or metatarsals. Bone matrix in the second and/or fifth metacarpals in the forelimbs with EDCs was thinner than that in the forelimbs with control. Dose- response of DES relative to incidence of abnormalities of bone was not clear. 7. The pulmonary functions were compared in babies born to dame treated with DES and those babies born to non-treated dame in rats. There was no significant difference between the two groups up to 9 weeks after birth. 8. Effects of various EDCs were investigated with respect to abilities to restructure in Dugesia japonica, cell culture derived from mice, and fetal mice. The relationships between the toxic effects of EDCs in non mammals and mammals do not always coincide.These results suggested that the development and architecture of the lung during maturation of fetuses in mice treated with EDCs was delayed based on the modeling of bone. There is no evidence of changes in pulmonary functions up to 9 weeks post partum. Bone morphology and ossification in fetus may serve as better biological markers to health assessment in EDCs toxicity. Less

本文从肺的发育、结构和生理功能等方面研究了内分泌干扰物（EDCs）的健康评价方法.研究结果：1.二乙基己烯雌酚（DES）处理母鼠所生的BALB/c雌性小鼠，对6种不同品系小鼠的增重均有显著的促进作用. DES组母鼠所生女婴胸腺重量和脾脏B细胞百分率均较对照组增加。3.与未治疗的小鼠相比，DES治疗的10日龄婴儿的肺中来自Clara细胞的CYP 2F 2、P450还原酶、胶原III和IV mRNA的表达减少。4. 6个品系母鼠经DES处理后所生仔鼠心肺组织的病理变化与相应对照组相比无显著性差异。5.用体外培养系统观察了3-甲基胆蒽（3 MC）对骨代谢的影响。 ...更多信息 em. 3 MC可抑制成骨细胞和破骨细胞的分化和增殖。结果提示3 MC可能对骨代谢起关键作用.在小鼠胚胎中研究了内分泌干扰物对骨形成的影响。内分泌干扰物处理的小鼠胚胎出现骨形态学异常和骨化延迟。颈椎、胸椎和四肢骨化延迟。在四肢中，在掌骨和/或跖骨中观察到延迟骨化。EDCs组第2和/或第5掌骨的骨基质较对照组薄。DES与骨异常发生率的剂量反应尚不清楚。7.比较DES组母鼠与对照组母鼠所生仔鼠的肺功能。在出生后9周内，两组之间没有显著差异。8.研究了各种内分泌干扰物对三角涡虫（Dugesia japonica）、小鼠细胞培养物和胎鼠重组能力的影响。EDCs对非哺乳动物和哺乳动物的毒性作用之间的关系并不总是一致的，这些结果表明，EDCs处理的小鼠胚胎在成熟过程中的肺的发育和结构延迟基于骨的模型。没有证据表明产后9周内肺功能发生变化。胎儿骨形态学和骨化情况可作为评价EDCs毒性的较好生物学指标。少

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