| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Tomomi National Institute of Public Health, Department of Nutrition and Biochemistry, Senior Research Officer, 栄養生化学部, 主任研究官 (00218439)
HIKAGE Sakari School of Dentistry, Health Sciences University of Hokkaido, Associate Professor, 歯学部, 助教授 (20134710)
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| Budget Amount *help |
¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 2001: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 2000: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Research Abstract |
The purpose of this reserch was to develop residual and leaching substances in dental organic materials as well as newly endocrine disrupter-sensitive cell lines with drug metabolizing function and to identify the gene expressed by bisphenol A(BPA). As orthodontic brackets made of PC, were immersed in human saliva, BPA as well as p-t-butylphenol(t-BuP) and p-cumylphenol(p-CP), which are polymerization regulatory agents,was leached from brackets into saliva. Furthermore, when brackets were immersed in heat-denatured saliva, the level of leached BPA was higher than those of saliva-immersion. Levels of residual BPA, t-BuP and p-CP was increased with the immersion time, suggesting that brackets immersed in saliva are depolymerized into BPA and t-BuP or p-CP and this depolymerization is not involve in enzymes in saliva such as esterases and lipases. There are necessary to evaluate the leachable and remaining chemical substances using saliva, and it is clear that the artificial saliva is ina
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dequate using alternatives of saliva. m-RNAs were extracted from T47D cells treated with BPA and fetal genital of mouse administered with 0.5, 5, 50 and 500 mg/kg/day of BPA from Day 3.5 of gestation and then the differential display was performed. Although there are differences between each controls and BPA-treated cell and mouse, only NADH dehydrogenase subunit 2 was identified. As thmus from mouse administered BPA is smaller than that of control, the effects of BPA on the production of cytokines were investigated. The producing ability of cytokines was inhibited by higher concentrations of BPA, whereas it was accelerated by lower concentrations of BPA. Analysing the effects of BPA on Jurkat human T cells, BPA was increased in concentrations of intracellular calcium ions pronto and various intracellular proteins were phosphorylated with BPA by SDS-PAGE examination. The cytotoxic effects of dental resin monomers after being metabolized by CYP3A4 and CYP3A7, using a colony formation assay and a neutral red assay were investigated. BPA and Bisphenol A glycidy1 methacrylate (Bis-GMA) and a positive control (Aflatoxine B1) were added separately to each well and cultured for 7 days. The resultant of IC_<50> values indicated that the monomers were not metabolically activated by CYP3A4 or CYP3A7 as compared to the control. These monomers act neither as activators nor as inhibitors of CYP3A4 and CYP3A7 Were confirmed. Analysing by reporter assay and Northan blot, Bis-GMA, BADGE 2H_2O and BPA induced CYP1A1 whereas BADGE inhibited its induction. However, this induction was markedly increased with 3-methylcholanthrene Less
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