Objective:To investigate the metabolites of polybrominated diphenyl ether 99(BDE-99)and its related cytochrome P450s in an in vitro system.Methods:Rat primary hepatocytes were isolated and treated with BDE-99 for 24-72 h.Metabolites were then extracted from the hepatocytes and media,and detected by GC/MS.Several mRNAs of metabolic enzymes were also extracted from the same cells and the gene expression levels were determined using quantitative real-time PCR.In addition,selected recombinant cytochrome P450s(CYPs) were expressed in a bacurovirus/sf9 system,and these were further used to explore the metabolism of BDE-99 in vitro.The parent depletion approach was used for screening the ability of CYPs to eliminate BDE-99.Results: A reductively debrominated metabolite,BDE-47,and three oxidative metabolites,2,4,5-tribromophenol,5-OH-BDE-47,and 5'-OH-BDE-99,were identified from the BDE-99-treated rat hepatocytes,whereas no MeO metabolite was detected in the system.RT-PCR analysis showed that CYP 3A23/3A1,1A2,and 2B1/2 were induced by BDE-99.Furthermore,using the heterological expressed CYP proteins in in vitro BDE-99 metabolism experiments we found that CYP1A2 and CYP3A4 showed the highest metabolic efficiency for BDE-99,with the metabolic clearance rates of CYP1A2 and CYP3A4 being 30.3%and 27.7%,respectively.CYP1A1 and CYP2A6 displayed relatively low clearance rates,while CYP2E1 seemed not to be associated with the BDE-99 metabolism.Conclusions:In our in vitro rat primary hepatocyte metabolism system,four metabolites of BDE-99 were identified,and CYP3A4 and CYP1A2 were demonstrated to be involved in the BDE-99 metabolism.
Huibin Dong Ziyin Li Xiaoming Man Jingping Zhou Huiyuan Lu Shoulin Wang
Low birth weight (LBW) is an important risk factor for neonatal and infant mortality and morbidity in adults..However,no large scale study on the prevalence of LBW and related maternal risk factors in China has been published.To explore the effects of maternal factors on LBW for term birth in China,we conducted a hospital-based retrospective study of 55,633 Chinese pregnancy cases between 2001 and 2008.Maternal sociodemographic data,history of infertility and contraceptive use were obtained.Their medical status and diseases during pre-pregnancy were examined by physical examination at the first antenatal care visit.Maternal medical status before childbirth and pregnancy outcomes,including body weight,infant gender,multiple pregnancy and congenital anomalies,were recorded.Univariate and multivariate logistic regression,and linear regression were used to investigate the relationship between maternal factors and term LBW.The general incidence of term LBW was 1.70% in the developed area of China.After preliminary analysis using the univariate model,low primary education,anemia,hypertensive disorders,placental previa,oligohydramnios and premature rupture of membrane were predicted as independent factors of term LBW in the multivariate model.Furthermore,the decrease in annual frquencies of these risk factors were major causes of gradual decline in the incidence of LBW (from 2.43% in 2001 to 1.21% in 2008).The study demonstrated that among maternal factors,primary education,anemia and hypertensive disorders could contribute to LBW for term birth even in the most developed area of China.
