急性时相血清淀粉样蛋白A和罗格列酮对内皮细胞白介素6、8基因表达的影响

目的观察急性时相血清淀粉样蛋白A（A-SAA）和罗格列酮（RGZ）对内皮细胞白细胞介素（IL）6和IL-8基因表达的影响。方法分别用不同浓度（0．5／μg／ml、5／Lg／μg）的A-SAA、RGZ（10μmol／L）处理ECV304内皮细胞8h、24h后抽提总RNA,用RT-PCR技术检测IL-6、IL-8 mRNA的表达。结果A-SAA能显著促进ECV304细胞IL-6、IL-8mRNA的表达,并呈剂量和时效依赖性（P〈0．01）。而RGz并不影响A—SAA对ECV304细胞IL-6和IL-8 mRNA表达的促进作用。结论A—SAA可通过促进内皮细胞IL-6、IL-8的表达和分泌,参与动脉粥样硬化的形成;RGZ并非通过影响A-SAA对内皮细胞IL-6和IL-8表达的促进作用发挥其抗炎、抗动脉粥样硬化的作用。     

蛋白激酶C抑制剂对脂多糖上调内皮细胞PAI-1表达的影响

目的 探讨脂多糖（LPS）对内皮细胞1型纤溶酶原灭活剂（PAI-1）表达的影响及蛋白激酶C（PKC）抑制剂在其中的可能作用。方法 用RT-PCR法检测PAI-1mRNA含量，Western印迹检测细胞内PAl．1蛋白含量，ELISA法测定培养上清液中PAI-1抗原含量。结果 0．01-10．0μg／ml LPS与ECV304共培养6h，能刺激PAI-1 mRNA呈剂量依赖性增加；经PKC抑制剂R032-0432预处理后，PAI-1 mRNA的表达水平较单纯LPS处理组显著降低，5μmol／L R032-0432预处理组PAI-1 mRNA水平甚至低于空白对照组。ECV304培养上清液和细胞内PAI-1蛋白的变化与mRNA水平呈平行关系。结论 在ECV304中，一定浓度的LPS可诱导PAI-1高表达，而PKC抑制剂能显著抑制LPS对PAI-1的诱导表达，甚至抑制PAI-1的基础表达水平。     

Ox-LDL对血管内皮细胞中ABCA1及单核细胞趋化因子的影响

目的研究在致动脉粥样硬化（AS）因子氧化型低密度脂蛋白（Ox-LDL）刺激下,人血管内皮细胞ECV304中腺苷三磷酸结合盒转运体A1（ABCA1）基因对炎性因子单核细胞趋化蛋白1（MCP-1）的调节作用,从而阐明ABCA1基因在AS发生中的作用机制。方法培养人血管内皮细胞ECV304,加入Ox-LDL（30 ng/ml）刺激3、6、12、24 h,以荧光定量RT-PCR检测ABCA1、MCP-1 mRNA表达量,Western蛋白印迹法和ELISA法检测ABCA1、MCP-1及IL-1β蛋白表达量;ABCA1的反义寡核苷酸（100 nmol/L）转染人血管内皮细胞,给予上述的Ox-LDL,同样方法测定上述指标的改变。结果人血管内皮细胞ECV304在给予Ox-LDL刺激后,ABCA1、MCP-1的mRNA和蛋白质水平及IL-1β蛋白质水平均增高;给予反义寡核苷酸转染3、6 h后,ABCA1、MCP-1 mRNA的表达降低,12、24h后ABCA1、MCP-1及IL-1β蛋白质的表达水平降低。结论在Ox-LDL作用下,血管内皮细胞中的ABCA1可能通过增加IL-1β的表达,促进MCP-1释放,从而在AS的早期发生中发挥作用。     

硒对人脐静脉内皮细胞ECV-304单核细胞趋化蛋白-1表达的影响

目的 观察硒对人脐静脉内皮细胞ECV-304单核细胞趋化蛋白-1(MCP-1)表达的影响方法分别用高葡萄糖、糖基化终末产物，高胰岛素和过氧化氢孵育人脐静脉内皮细胞ECV-304；在先加入100nmol／L硒后，再给予以上4种因素．分别检测人脐静脉内皮细胞ECV0304MCP-1mRNA的表达并比较。结果 4种因素均可作为独立因素，导致人脐静脉内皮细胞ECV304MCP-1mRNA表达量增加：硒能抑制4种因素所致的MCP-1mRNA表达。结论 硒抑制MCP-1 mRNA在人脐静脉内皮细胞ECV-304中的表达。     

反应停对肺腺癌细胞株诱导的血管内皮细胞增殖的影响

目的探讨反应停对肺腺癌细胞株诱导的血管内皮细胞增殖的影响。方法用噻唑兰法检测不同浓度反应停对血管内皮细胞株ECV304（ECV304细胞）、肺腺癌细胞株SPC—A1（SPC—A1细胞）及其诱导的血管内皮细胞ECV304增殖的影响。结果反应停浓度为8．0和80．0μg／ml时对ECV304细胞增殖有抑制作用（P〈0．05）;不同浓度反应停对SIC-A1细胞增殖无影响;经8．0和80．0μg／ml反应停作用后SIC-A1细胞条件培养液对ECV304细胞增殖有抑制作用（P均〈0．05）,其细胞生长抑制率分别为5．19％、12．49％。结论反应停对SPC-A1细胞诱导的ECV304细胞增殖有抑制作用。     

单核—巨噬细胞和ECV304内皮细胞表达死亡相关蛋白

为研究单核——巨噬细胞和ECV304细胞是否表达死亡相关蛋白以及影响死亡相关蛋白表达的因素。分别用氧化型低密度脂蛋白(100mg／L)孵育THP-1细胞，H2O2(1mmol／L)孵育ECV304细胞，用逆转录聚合酶链反应检测死亡相关蛋白mRNA的表达。结果发现，THP-1细胞及ECV304细胞均表达死亡相关蛋白，氧化型低密度脂蛋白和H2O2能分别诱导THP-1细胞和ECV304细胞死亡相关蛋白mRNA表达增高。实验结果提示死亡相关蛋白可能参与调节氧化应激诱导的单核—巨噬细胞和内皮细胞的凋亡。     

阿托伐他汀对ox—LDL诱导的大鼠血管平滑肌细胞妊娠相关血浆蛋白-A的影响

目的观察阿托伐他汀对氧化低密度脂蛋白（ox—LDL）诱导的大鼠血管平滑肌细胞（VSMCs）妊娠相关血浆蛋白-A（PAPP—A）的影响,探讨阿托伐他汀抗动脉粥样硬化（AS）的机制。方法SD大鼠VSMCs体外原代培养,用不同浓度ox-LDL（75、150、300μg／ml）处理不同时问（2,12 and 24h）构建VSMC损伤模型。使用RT—PCR及Western Blotting测定VSMCs PAPP-A mRNA和蛋白的表达。观察阿托伐他汀干预后,VSMC PAPP—A mRNA和蛋白表达的变化。结果ox—LDL干预后,VSMCs PAPP—A mRNA和蛋向的表达呈剂量和时间依赖性升高;300μg／ml ox—LDL处理12h和24h后,PAPP—A mRNA和蛋白表达水平较对照组明显升高（P〈0．01）;而阿托伐他汀干预后,PAPP—A mRNA和蛋白表达明显下降（P〈0．01）。结论阿托伐他汀可以调控ox—LDL诱导的PAPP-A mRNA和蛋白表达,提示其抗AS的机制与PAPP—A有关。     

果蝇样受体4介导游离脂肪酸调节人血管平滑肌细胞单核细胞趋化蛋白-1的表达

目的探讨软脂酸对人主动脉血管平滑肌细胞（HA—VSMC）单核细胞趋化蛋白-1（MCP-1）基因表达的调节及果蝇样受体4（TLR4）信号通路的作用。方法采用不同剂量的软脂酸（100、200、400μmol/L）处理HA—VSMC6、12、24h,采用实时荧光定量聚合酶链反应（PCR）检测细胞MCP．1mRNA表达,酶联免疫吸附实验（ELISA）检测MCP-1蛋白表达,观察软脂酸调节MCP-1表达的剂量依赖关系和时间效应;采用蛋白激酶C（PKC）抑制剂白屈菜红碱、磷脂酰肌醇3激酶（P13K）抑制剂wortmannin、神经酰胺抑制剂myriocin和核因子KB（NF—KB）抑制剂parthenolide分别处理细胞30min,再加入软脂酸（400μmol/L）处理细胞6h后,实时荧光定量PCR检测MCP-1mRNA的表达水平,ELISA检测MCP-1的蛋白表达水平,研究软脂酸调节MCP-1表达依赖的信号通路;构建TLR4短发夹RNA（shRNA）腺病毒pGSadeno-TLR4并感染HA—VSMC沉默TLR4基因表达,实验同时设空白对照组（PBS缓冲液）和对照病毒（pGSadeno-GFP）组。细胞感染96h后更换培养基,再加入软脂酸（400μmoL／L）处理细胞6h,采用实时荧光定量PCR检测MCP-1mRNA表达水平,ELISA检测MCP-1的蛋白表达水平。提取细胞核蛋白,采用ELISA检测NF—KBp65亚基活性,观察TLR4／NF-KB通路在软脂酸调节HA-VSMCMCP-1基因表达中的作用。组间均数比较采用单因素方差分析。结果采用软脂酸处理细胞6h后,对照组及100、200和400μmoVL软脂酸组MCP-1mRNA表达分别为1．00±0．02、3．30±2．84、8．21±4．31和11．25±2．73（F=7．57,P〈0．05）;MCP-1蛋白表达分别为（127±10）、（147±10）、（163±18）和（194±14）ng／L（F=7．81,P〈0．05）。软脂酸可促进HA-VSMCMCP-1mRNA和蛋白表达且具有明显的剂量依赖关系。细胞培养12h和24h后,随着软脂酸浓度的增加,MCP-1mRNA和蛋白表达水平呈逐渐增加趋势,但时间效应则不明显。采用不同的信号通路抑制剂和软脂酸处理细胞6h后,对照组、软脂酸组、软脂酸＋parthenolide组、软脂酸＋白屈菜红碱组、软脂酸＋wortmannin组和软脂酸＋myriocin组MCP-1mRNA表达分别为1．00±0．02、10．80±1．23、3．49±0．28、10．84±0．24、11．24±0．27和10．62±0．36（F=1313．07,P〈0．05）;MCP-1蛋白表达分别为（132±8）、（218±12）、（152±4）、（213±12）、（225±7）和（226±9）ng／L（F=106．83,P〈0．05）。成功地构建并获得TLR4shRNA腺病毒pGSadeno—TLR4,采用pGSadeno-TLR4感染HA—VSMC阻断TLR4信号后,软脂酸＋pGSadeno．TLR4组的NF—KB065结合活性、MCP-1mRNA和蛋白表达均显著低于软脂酸组[分别为0．48±0．12比1．24±0．16、1．88±0．33比10．80±1．23、（154±10）比（218±12）ng／L;F=591．86、659．16、118．37,均P〈0．01]。而对照病毒pGSadeno．GFP对软脂酸诱导的NF—KB065结合活性和MCP：I表达均无明显影响。结论TLR4／NF—KB信号通路介导了软脂酸诱导的人主动脉血管平滑肌细胞MCP-1基因表达。     

氧化低密度脂蛋白通过血凝素样氧化低密度脂蛋白受体1诱导血管内皮细胞粘附分子的表达

目的探讨血凝素样氧化低密度脂蛋白受体1（LOX-1）在氧化低密度脂蛋白（ox—LDL）诱导血管内皮细胞粘附分子表达中的作用。方法用不同浓度ox-LDL培养人脐静脉内皮细胞（HUVECs）,用RrealtimeRT—PCR测定LOX-1 mRNA的表达;RT—PCR测定细胞间粘附分子1（ICAM-1）、血管细胞粘附分子1（VCAM-1）以及E选择素的mRNA表达;用Westernblot测定LOX-1、ICAM-1、VCAM-1以及E选择素蛋白的表达,观察ox-LDL对血管内皮细胞粘附分子表达的影响。HUVECs预先用聚肌苷酸[poly（I）]和爱兰苔胶处理,再用ox—LDL培养,再分别测定上述粘附分子的表达水平,比较加入LOX-1阻断剂前后粘附分子表达的变化。结果ox-LDL各剂量组皆可上调LOX-1、ICAM-1、E选择素的mRNA和蛋白表达（P〈0．01）,在10～50μm/ml剂量范围内呈现明显的剂量一效应关系（P〈0．01）,但ox—LDL对VCAM-1的表达没影响。HUVECs预先与250μg／ml的poly（Ⅰ）或爱兰苔胶作用2h,然后加入50μg/ml的ox—LDL作用24h。poly（Ⅰ）和爱兰苔胶都能抑制ox—LDL诱导的LOX-1、ICAM-1和E选择素的mRNA和蛋白表达水平,与未阻断组相比,差异皆有统计学意义（P〈0．01）。结论ox—LDL可以上调血管内皮细胞粘附分子的表达,LOX-1受体阻断剂可以部分阻断ox—LDL的上调作用,ox-LDL诱导血管内皮细胞粘附分子的表过是通过LOX-1介导的。     

维生素C对AS2O3抑制肺癌A549细胞增殖、诱导细胞凋亡作用的影响及机制

目的探讨维生素C对三氧化二砷（AS2O3）抗癌作用的影响及其可能机制。方法将体外培养的肺腺癌A549细胞随机分为6组,其中对照组不行特殊处理,AS2O3 1—3组分别加入0．4、4．0、40μg/ml的AS2O3,维生素C组加入400μg／ml的维生素C,联合组加入400μg／ml维生素C＋0．4μg／ml AS2O3。采用缩胆囊素八肽（CCK-8）法及克隆形成实验检测细胞生长情况（A值）,用流式细胞仪检测细胞周期及凋亡率,用RT-PCR方法检测Caspase-3 mRNA、多药耐药相关蛋白基因1（MRP1）mRNA、多药耐药基因1（MDR1）mRNA表达情况（维生素C组）。结果联合组及AS2O3 2、3组A值均显著低于对照组及AS：O3组、维生素C组,且随作用时间延长逐渐降低（P〈0．05）;联合组细胞集落显著少于其他五组,G0／G1期所占比例及凋亡率均显著高于其他五组（P〈0．05）;维生素C组Caspase-3 mRNA、MDR1 mRNA表达升高（P〈0．05）、MRP1 mRNA表达无明显变化（P〉0．05）。结论维生素C对As2O3抗肺腺癌A549细胞的作用具有协同性,可能机制为上调Caspase-3表达;两者联用可望成为低毒高效的化疗组合。     

1-Naphthyl isocyanate and 1-naphthylamine as metabolites of 1-naphthylisothiocyanate

Abstract: The importance of the bioactivation of 1-naphthylisothiocyanate was studied. Forty minutes after 1-naphthylisothiocyanate administration to rats, bile was collected over a 2.5-h period; the liver was then excised and homogenized. 1-naphthylisothiocyanate and its metabolites in bile and liver of rats were identified and quantified using coupled gas chromatography-mass spectrometry. Three main compounds were found in all 1-naphthylisothiocyanate-treated animals. They were identified as 1-naphthyl isocyanate, 1-naphthylamine and the parent compound, 1-naphthylisothiocyanate. When rats were given cycloheximide, which attenuates 1-naphthylisothiocyanate toxicity, 30 min before 1-naphthylisothiocyanate (300 mg/kg), 1-naphthyl isocyanate concentration was significantly lower than in rats receiving only 1-naphthylisothiocyanate. The appearance of 1-naphthylamine was also inhibited by cycloheximide, although not to the same extent as 1-naphthyl isocyanate. On the other hand, phenobarbital, which potentiates 1-naphthylisothiocyanate hepatotoxicity, enhanced 1-naphthyl isocyanate and 1-naphthylamine formation. It is suggested that 1-naphthyl isocyanate, 1-naphthylamine and the highly reactive sulfur released from 1-naphthylisothiocyanate might be involved in the hepatotoxic effect of 1-naphthylisothiocyanate.     

Genetic link with cholelithiasis among pediatric SCA Tunisian patients: Examples of UGT1A1, SLCO1A2 and SLCO1B1

Aims and background: Hyperbilirubinemia is often observed in chronic hemolysis and results in the formation of pigment cholelithiasis that could be increased by the presence of defected enzymes involved in the bilirubin metabolism. Indeed, this is the first report that interested in the study of polymorphisms in genes encoded for enzymes involved in the bilirubin metabolism: rs 4149056 of SLCO1B1 and rs4149000 of SLCO1A2 in combination with rs8175347 and rs887829 of UGT1A1 in order to find a correlation between the polymorphisms studied and the presence of gallstones in a population of sickle cell anemia (SCA) pediatric Tunisians.

Material and methods: Our study involved 102 unrelated Tunisian subjects. All SCA patients are children (less than 16 years old) and were characterized by hyperbilirubinemia and 52 of them have cholelithiasis. The polymorphisms of the candidate genes were analyzed for all subjects by PCR/sequencing. Genotype and allele frequencies between cases and controls were compared using Pearson's chi-square test with a significance threshold of P?<?0.05 (compare 2, version 1.02).

Results: The novelty of this report is that children carrying the combined genotype of the rs studied: (TA7TA7)/TT/TC/GA have a higher risk to develop gallstones (P?=?0.0027, RR?=?18.27 (20.0061–915.28)).

Conclusion: Altogether our data provide the implication of UGT1A1 and SLCO1A2 in sickle cell anemia-related cholelithiasis.     

甲型H1N1与季节性H1N1流感病毒血凝素基因比较分析

目的分析泰安市2008～2009年度季节性流感与2009年度甲型H1N1流感病原学检测结果 ,比较季节性H1N1与甲型H1N1血凝素基因变异情况。方法选择国家级流感监测哨点医院以及暴发疫情的疫点,采集流感样病例的鼻咽拭子标本,通过RealtimePCR进行病毒检测,用MDCK细胞进行病毒分离,通过RT-PCR扩增血凝素HA1片段的基因并测序,利用生物信息学进行序列分析。结果 2008～2009年共检测鼻咽拭子标本283份,分离出流感病毒33株,分离阳性率为11.67%,其中季节性H1N1亚型31株。2009年5月1日～12月31日,检测鼻咽拭子标本996份,流感核酸检测阳性417份,阳性率为41.86%,其中甲型H1N1337份,季节性H1N1亚型1份。6株季节性H1N1病毒均在多个氨基酸位点上发生变异,与疫苗株A/Brisbane/59/2007(H1N1)比较,有11个位点发生了突变,其中5个位点位于抗原决定簇上;测序成功的6株甲型H1N1病毒在多个氨基酸位点发生变异,与疫苗株A/California/07/2009(H1N1)比较,有6个位点发生突变,其中1个位点位于抗原决定簇的B区。结论 2008～2009年度季节性H1N1为优势株,甲流暴发后,甲型H1N1成为绝对优势毒株。季节性H1N1分离株有多处氨基酸替换,抗原决定簇B区变异频繁;甲型H1N1病毒分离株的基因有变异,但关键位点第222位仍为D(天冬氨酸),与疫苗株相比抗原决定簇的关键位点变化不大。     

Cytochrome 1A1 and 1B1 gene diversity in the Zanzibar islands

Amodiaquine (AQ) is a 4‐aminoquinoline widely used in the treatment of malaria as part of the artemisinin combination therapy (ACT). AQ is metabolised towards its main metabolite desethylamodiaquine mainly by cytochrome P450 2C8 (CYP2C8). CYP1A1 and CYP1B1 play a minor role in the metabolism but they seem to be significantly involved in the formation of the short‐lived quinine‐imine. To complete the genetic variation picture of the main genes involved in AQ metabolism in the Zanzibar population, previously characterised for CYP2C8, we analysed in this study CYP1A1 and CYP1B1 main genetic polymorphisms. The results obtained show a low frequency of the CYP1A1*2B/C allele (2.4%) and a high frequency of CYP1B1*6 (approximately 42%) followed by CYP1B1*2 (approximately 27%) in Zanzibar islands. Genotype data for CYP1A1 and CYP1B1 show a low incidence of fast metabolisers, revealing a relatively safe genetic background in Zanzibar’s population regarding the appearance of adverse effects.     

甲型H1N1流感合并肺炎的临床特点分析

目的通过对甲型H1N1流感合并肺炎的临床特点的分析。方法分析2009年月10月-2010年3月在我院入住的29例甲型H1N1流感合并肺炎患者的临床表现、实验室检查及胸部CT等资料。结果本组病例男性16例,女性13例。3例妊娠,13例合并有基础疾病。所有病例均有流感样前驱症状,呼吸道主要症状为发热、干咳少痰,严重者气短、呼吸困难、咯血。合并细菌感染时咯脓痰。肺部听诊无啰音或少啰音,合并哮喘时有哮鸣音,合并细菌感染时可有湿啰音。实验室检查65%白细胞不高或降低,41%心肌酶升高,58.6%存在低氧血症,35%呼吸衰竭。影像学表现多种多样：65.5%主要为单侧或双侧棉团样、团片样边界模糊高密度渗出影伴肺实变,其内见充气支气管征,病变沿支气管血管束分布。轻症及早期较局限,重症者及晚期病变融合呈双肺多发弥漫性改变。少数呈大叶及小叶性肺炎表现。预后大多良好,病死率6.9%。主要死亡原因为呼吸衰竭及大咯血。结论甲型H1N1流感合并肺炎是以甲型H1N1流感病毒肺炎为主要疾病的多种肺炎构成。甲型H1N1流感病毒肺炎临床表现具有流感病毒肺炎共性特点,其影像学表现有一定特征性。     

Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin

Abstract:  Administration of melatonin to rodents decreases the incidence of tumorigenesis initiated by benzo[ a ]pyrene or 7,12-dimethylbenz[ a ]anthracene, which requires bioactivation by cytochrome P450 enzymes, such as CYP1A1, CYP1A2 and CYP1B1, to produce carcinogenic metabolites. The present study tested the hypothesis that melatonin is a modulator of human CYP1 catalytic activity and gene expression. As a comparison, we also investigated the effect of melatonin on the catalytic activity of CYP2A6, which is also a procarcinogen-bioactivating enzyme. Melatonin (3–300 μ m ) decreased 7-ethoxyresorufin O -dealkylation catalyzed by human hepatic microsomes and recombinant CYP1A1, CYP1A2 and CYP1B1, whereas it did not affect coumarin 7-hydroxylation catalyzed by hepatic microsomes or recombinant CYP2A6. Melatonin inhibited CYP1 enzymes by mixed inhibition, with apparent K _i values (mean ± S.E.M.) of 59 ± 1 (CYP1A1), 12 ± 1 (CYP1A2), 14 ± 2 (CYP1B1) and 46 ± 8 μ m (hepatic microsomes). Additional experiments indicated that melatonin decreased benzo[ a ]pyrene hydroxylation catalyzed by hepatic microsomes and CYP1A2 but not by CYP1A1 or CYP1B1. Treatment of MCF-10A human mammary epithelial cells with melatonin (up to 300 μ m ) did not affect basal or benzo[ a ]pyrene-inducible CYP1A1 or CYP1B1 gene expression. Consistent with this finding, melatonin did not influence reporter activity in aryl hydrocarbon receptor-dependent pGudluc6.1-transfected MCF-10A cells treated with or without benzo[ a ]pyrene, as assessed in an in vitro cell-based luciferase reporter gene assay. Overall, melatonin is an in vitro inhibitor of human CYP1 catalytic activity, and it may be useful to develop potent analogues of melatonin as potential cancer chemopreventive agents that block CYP1-mediated chemical carcinogenesis.     

Role of CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 genes in the susceptibility to acute leukemias

Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI = 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% CI = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% CI = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% CI = 1.4-9.4 and OR = 3.9, 95% CI = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1*2A, and GSTT1"null" variants and the risk of acute leuke-mia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 "null" variants to the development of acute leukemias.