Placental Transfer of Conjugated Bisphenol A and Subsequent Reactivation in the Rat Fetus

Background : Bisphenol A (BPA), a well-known endocrine disruptor, is highly glucuronidated in the liver, and the resultant BPA-glucuronide (BPA-GA) is excreted primarily into bile. However, in rodents, prenatal exposure to low doses of BPA can adversely affect the fetus, despite the efficient drug-metabolizing systems of the dams. The transport mechanisms of BPA from mother to fetus are unknown. Objectives : To test our hypothesis that BPA-GA—an inactive metabolite—is passed through the placenta to the fetus, where it affects the fetus after reactivation, we investigated the placental transfer of BPA-GA and reactivation to BPA in the fetus. Methods : After performing uterine perfusion with BPA-GA in pregnant rats, we examined the expression and localization of the placental transporters for drug metabolites in the perfusate by reverse-transcriptase polymerase chain reaction and immunohistochemistry. We also investigated the deconjugation of BPA-GA in the fetus and examined uridine 5′-diphospho-glucuronosyltransferase (UGT) activity toward BPA and the expression of UGT isoforms in fetal liver. Results : We detected BPA-GA and deconjugated BPA in the fetus and amniotic fluid after perfusion. In the trophoblast cells, organic anion-transporting polypeptide 4a1 (Oatp4a1) was localized on the apical membrane, and multidrug resistance-associated protein 1 (Mrp1) was localized to the basolateral membrane. We observed deconjugation of BPA-GA in the fetus; furthermore, we found the expression of UGT2B1, which metabolizes BPA, to be quite low in the fetus. Conclusions : These results demonstrate that BPA-GA is transferred into the fetus and deconjugated in the fetus because of its vulnerable drug-metabolizing system

Dose Linearity and Linear Energy Transfer Dependence of Cr-doped Al2O3 Ceramic Thermoluminescence Detector

Cr doped alumina (Al2O3:Cr) ceramic TLD suitable to be a 2D imaging device in radiation therapy. In this work, we investigated the dose linearity in the dose level of radiotherapy and the LET dependence of Al2O3:Cr ceramic TLD using several HCP beams. Al2O3:Cr ceramic TLD had good linearity with the irradiated dose. But it had a large LET dependence and it was difficult to apply to dose measurement in HCP therapy directly. However, the combination of Al2O3:Cr ceramic TLD and Cr non-doped Al2O3 ceramic TLD may be expected to be applied to measurement of LET distribution using these different LET dependence