DNA adducts in fish following an oil spill exposure

On 12 December 1999, one third of the load of the Erika tanker, amounting to about 10,000 t crude oil flowed into sea waters close to the French Atlantic Coast. This oil contained polycyclic aromatic compounds (PAC) that are known to be genotoxic. Genotoxic effects induce DNA adducts formation, which can thus be used as pollution biomarkers. Here, we assessed the genotoxic impact of the “Erika” oil spill by DNA adducts detection in the liver of immature fishes (Solea solea) from four locations of the French Brittany coasts. Two months after the spill, a high amount of DNA adducts was found in samples from all locations, amounting to 92–290 DNA adduct per 10⁹ nucleotides. Then total DNA adduct levels decreased to reach about 50 adducts per 10⁹ nucleotides nine months after the spill. In vitro experiments using human cell cultures and fish liver microsomes evidence the genotoxicity of the Erika fuel. They also prove the formation of reactive species able to create DNA adducts. Furthermore, in vitro and in vivo DNA adducts fingerprints are similar, thus confirming that DNA adducts are a result of the oil spill.     

Perinatal hepatic infarction in twin–twin transfusion

We report a case of a twin pregnancy which was complicated by a twin–twin transfusion in which the recipient twin was noted to have an intra-abdominal echogenic mass. This twin died at two days of age of hepatic infarction. The donor twin was healthy at birth, at thirty weeks' gestation, and did not have any subsequent problems. Fetal intra-abdominal echogenicity may be a marker of hepatic infarction. Copyright © 2002 John Wiley & Sons, Ltd.     

挥发性甲基硅氧烷的体外代谢行为

挥发性甲基硅氧烷(volatile methyl siloxanes,VMSs)的高产量、环境广泛存在性和毒性使其成为备受关注的新型环境污染物.VMSs在生物体中的代谢速率是决定其生物富集性的关键因子,但是目前还没有此类物质代谢速率的测试和报道.利用了鲈鱼和鹌鹑肝微粒体的体外代谢体系,测定了16种常见VMSs(D3~D6和L3~L14)的固有清除率.VMSs在鲈鱼肝微粒体中的固有清除率为0~0.031 m L·(h·mg)-1.D5在鲈鱼肝微粒体中难以代谢,与其在水生食物网中呈现显著生物放大性相一致;L4~L14均难以代谢,表明链状VMSs可能具有较高的生物富集性.VMSs在鹌鹑肝微粒体中的固有清除率[0.25~1.7m L·(h·mg)-1]显著高于鲈鱼,较快的代谢速率表明D3~D6和L3~L14在鸟类中可能不存在明显的生物放大现象;应用B[a]P作为基准物质校正代谢速率的测定误差,分析VMSs代谢速率的构效关系,发现影响VMSs在鸟类肝微粒体中代谢速率的主要因素为疏水性和电性参数.     

Effect of chronic exposure to cadmium on hepatic drug metabolism

Abstract

In an attempt to examine the chronic effect of low levels of cadmium on hepatic drug‐metabolizing enzyme system, an experiment was carried out in which growing male rats were given 0, 5, 10, and 2 0 ppm of cadmium in drinking water for a period of 8 weeks. An ip administration of a hypnotic dose of pentobarbital to the cadmium‐treated and the control rats 2 4 hr following the termination of the experiment exhibited that there was no significant difference in the drug metabolism in control and any of the treated groups. Next, liver microsomes were isolated from animals in all groups to study their ability to metabolize drugs in vitro. The results indicated that the activity of benzphetamine N‐demethylase and aniline hydroxylase, and the concentration of microsomal cytochrome P‐450 were almost identical in the control and treated groups. On the other hand, a single ip dose of cadmium (2 mg/kg) caused significant decrease in the in vivo and in vitro microsomal drug metabolism. These results suggest that although a single ip dose of cadmium (2 mg/kg) causes significant inhibition of drug metabolism, chronic exposure to cadmium up to 2 0 ppm in drinking water over a period of 8 weeks is unlikely to affect hepatic drug metabolism.     

PFOS致大鼠肝毒性及其作用机制研究

通过全氟辛烷磺酸(perfluomoctane sultanate,PFOS)大鼠灌胃染毒实验评价PFOS对肝功能的影响,探讨PFOS肝毒性反应的潜在机制与可能途径。将Sprague Dawley (SD)雄性大鼠随机分为3组,分别以0 mg·kg~(-1)、5 mg·kg~(-1)和10 mg·kg~(-1)PFOS灌胃染毒28 d。以HE和油红染色法观察大鼠肝脏形态改变。ELISA法测定各组谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate transaminase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)含量变化。化学比色法测定肝匀浆脂代谢水平和氧化产物含量。RT-PCR法检测肝脏内氧化应激以及脂代谢相关基因表达水平。结果表明,PFOS暴露大鼠体重显著降低而肝脏系数显著增加(P0.05),与对照组相比PFOS组血清肝功能酶均出现随PFOS浓度增加而升高(P0.05)。同时大鼠肝脏谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-px)和丙二醛(malondialdehyde,MDA)水平在高剂量组显著升高(P0.05),超氧化物歧化酶(superoxide dismutase,SOD)含量先显著升高(P0.05)后显著降低(P0.05)。且肝脏中脂代谢水平也随PFOS浓度的增加而出现显著改变(P0.05)。PFOS组基因表达均较对照组显著上升(P0.05)。以上结果说明PFOS具有明显的肝毒性作用,可影响肝脂代谢水平,这可能与PFOS引起的氧化应激所导致的损伤有关。     

羟基多溴联苯醚(OH-PBDEs)小鼠肝脏微粒体体外代谢及对雌激素代谢的影响研究

羟基化多溴联苯醚(OH-PBDEs)是一类具有内分泌干扰效应的酚类化合物,以小鼠肝脏微粒体作为研究对象,考察了OH-PBDEs的体外代谢行为及对雌激素代谢的影响。研究结果发现,4种OH-PBDE均能够代谢,其代谢率大小为6-OH-BDE-996’-OH-BDE-996-OH-BDE-1375’-OH-BDE-99,表明羟基官能团(-OH)与醚键及溴原子处于邻位时,表现出较高的代谢率; 4种OH-PBDE对3种天然雌激素包括雌酮(E1)、17β-雌二醇(E2)、雌三醇(E3)的代谢表现出不同作用,整体来说,对E1和E2代谢随着OH-PBDE浓度的增加抑制作用逐渐增强,对E3代谢则表现出促进作用,但是对人工合成的雌激素17α-炔雌醇(EE2)无明显影响;对E2代谢产物2-羟基雌二醇(2-OH-E2)的生成量定量表征表明,除6-OH-BDE-99促进了2-OH-E2的生成量,其余3种OH-PBDE随实验添加浓度的增加,抑制了2-OH-E2的生成量,这可能与酶介导的不同代谢机制有关。     

含油废水对鲤鱼肝脏微粒体芳烃羟化酶的活性诱导研究

以鲤鱼肝脏微粒体为实验体系,运用体外实验方法,研究三种含油废水对芳烃羟化酶的活性影响,结果表明,三种含油废水对芳烃羟化酶活性都表现出不同程度的诱导,随着含油量的增大,AHH活性升高,并有相似的变化趋势。芳烃羟化酶活性升高可以作为监测含油废水对水体污染的一种生物指标。     

An evaluation of the cytochrome P450 inhibition potential of selected pesticides in human hepatic microsomes

The goal of this work was to study the ability of 18 pesticides to inhibit selective model activities for all major xenobiotic-metabolizing enzymes, namely CYP1A1/2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. Generally organophosphorus insecticides were the most potent and extensive inhibitors, especially towards CYP1A1/2 (IC₅₀ values of chlorpyrifos, fenitrothion and profenofos ～3 μ M), CYP2B6 (IC₅₀ values of chlorpyrifos and fenitrothion 2.5 μ M), CYP2C8 (fenitrothion 4.3 μ M), CYP2C9 (fenitrothion and malathion 4.8 and 2.5 μ M, respectively), CYP2D6 (chlorpyrifos and phenthoate ～ 3 μ M) and CYP3A4 (chlorpyrifos, fenitrothion and phenthoate 3–4 μ M). Otherwise there were quite considerable differences in potency and extent of inhibition between different organophosphates. Pyrethroids were in general very weak or inactive. Deltamethrin and fenvalerate were potent inhibitors of CYP2D6 (IC₅₀ values of ～ 3 μ M) while lambda-cyhalothrin potently inhibited both CYP2D6 and CYP3A4-mediated activities (IC₅₀'s about 3–4 μ M). Some pesticides caused relatively potent inhibitions sporadically (carbendazim, CYP2D6, IC₅₀ = 12 μ M; atrazine, CYP3A4, IC₅₀ = 2.8 μ M; glyphosate, CYP2C9, IC₅₀ = 3.7 μ M; hexaflumuron, IC₅₀ = 6.0 μ M). With the exceptions of alpha-cypermethrin, cypermethrin, isoproturon, carbaryl and abamectin, most pesticides inhibited relatively potently at least one CYP-selective activity, which may have relevance for potential interactions in occupational exposures and for further studies on the CYP-associated metabolism of respective pesticides.     

布洛芬对黄颡鱼I相代谢酶及其抗氧化系统的影响

使用环境相关浓度水平(0.05、0.5、5、50 μg· L-1)的布洛芬(Ibuprofen,IBU)对黄颡鱼进行水体暴露,研究IBU对黄颡鱼Ⅰ相代谢酶及其抗氧化系统的影响.结果表明,随着暴露时间的延长,IBU对黄颡鱼肝脏Ⅰ相代谢P450酶系的氨基比林-N-脱甲基酶(APND)、红霉素-N-脱甲基酶(ERND)、7-乙氧基-异吩噁唑酮-脱乙基酶(EROD)和Ⅱ相代谢谷胱甘肽硫转移酶(GST)均表现出先诱导后抑制的作用.暴露24 h时,IBU浓度为5 μg· L-1实验组对Ⅰ相代谢酶APND和ERND的诱导程度最大.当暴露时间达到168 h时,0.5 μg·L-1浓度组中APND和ERND活性均受到极显著抑制.Ⅰ相代谢酶EROD活性在暴露24 h后,除0.05 μg· L-1浓度组无明显变化外,其它浓度组皆受到显著诱导,随着暴露时间延长到168 h时,逐渐恢复到初始水平.GST活性在暴露24 h后,除0.05 μg·L-1浓度组外,其它浓度组均受到最大程度的诱导,过氧化氢酶(CAT)在暴露168 h时被显著诱导.各浓度组丙二醛(MDA)含量在暴露24 h时较对照组显著下降,72 h时其含量达到最高值.其中,ERND响应较为敏感,适合作为布洛芬暴露的生物标记物.     

Ultrasonographic diagnosis of a fetal abdominal mass: A case of a mesenchymal liver hamartoma and a review of the literature

A case of a prenatally recognized hepatic mesenchymal hamartoma is presented and the literature reviewed. These tumors are benign and usually present in early infancy with symptoms that are related to the mass effect on adjacent organs. Radiologic methods used in the past to image this tumor include angiography and ultrasound. However, there is no specific radiologic finding, and, therefore, the diagnosis is usually made during surgery. Once the tumor is removed, the prognosis is generally good. With the increasing use of high resolution ultrasound in prenatal diagnosis, this rare tumor should be considered in the differential diagnosis of any multicystic mass found in the fetal abdomen. The recognition of a mass should then alert the physician to the need for early neonatal intervention.