淡色库蚊XND-P450基因cDNA全长克隆及表达

【目的】克隆淡色库蚊氯菊酯抗性相关XND-P450基因,并对其进行生物信息学分析,研究其在敏感品系和抗性品系淡色库蚊中表达量的差异,为阐明XND-P450的功能和抗性机制奠定基础。【方法】依据淡色库蚊抗性品系与敏感品系差异表达的EST片段设计PCR引物,采用RACE技术克隆淡色库蚊氯菊酯抗性相关基因XND-P450全长cDNA序列,并对其进行生物信息学分析;采用半定量PCR技术,对XND-P450基因在敏感品系和抗性品系淡色库蚊中的表达量差异进行检测。【结果】经过克隆获得长度为1 679bp的淡色库蚊氯菊酯抗性相关基因XND-P450全长cDNA,编码523个氨基酸。生物信息学分析表明,该基因与致倦库蚊、埃及伊蚊CYP450基因的同源性在70%以上,其编码蛋白相对分子质量为33 244.9u,理论等电点为8.10,属于不稳定的亲水蛋白,氨基酸序列与致倦库蚊及冈比亚按蚊CYP450蛋白的同源性在40%以上。半定量PCR电泳分析显示,抗性品系淡色库蚊中的XND-P450基因表达量较敏感品系高。【结论】克隆了淡色库蚊氯菊酯抗性相关XND-P450基因,该基因在抗性品系淡色库蚊中的表达量高于敏感品系,推测其与氯菊酯抗性相关。

Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle,Fujian Province

AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in the development of gastric cancer in Changle county, Fujian Province.

Insecticide induction of O-demethylase activity and expression of cytochrome P450 genes in the red imported fire ant (Solenopsis invicta Buren)

The red imported fire ant （Solenopsis invicta） is a global major invasive pest, and has caused significant economic, social and environmental impacts since its invasion to mainland of China in 2004. To date, chemical control has been the most effective measure. However, the long-term use of chemicals would lead to an unexpected rebound. To understand the risks and explore the mechanisms of detoxification or induction to insecticides in S. invicta, the O-demethylase activity and expression of cytochrome P450 genes of workers and queens, and the effects of chlorpyrifos and fipronil exposure in workers were investigated. Biochemical assays showed the O-demethylase activity of cytochrome P450 was significantly higher in workers than in queens （1.66-fold）, and was significantly induced in workers exposed to chlorpyrifos and fipronil, reaching a maximum （3.00- and 1.95-fold） at 48 h and then decreasing dramatically compared to controls （exposed to acetone counter- part）. The relative expression levels of 12 cytochrome P450 expressed sequence tags （ESTs） in workers were significantly higher than in queens （from 2.3- to 36.4-fold）. Multiple cytochrome P450 genes （except 9E4） were co-up-regulated （from 1.5- to 2.86-fold） in workers exposed to fipronil. These results indicated that the increased O-demethylase activity may result from the increased transcription levels of cytochrome P450 related to detoxification of insecticides in S. invicta. It appears that cytochrome P450 plays an important role in enhanced metabolic detoxification of insecticides. At the same time, it also provides the theoretical basis for resistance management and rational usage of insecticides to control S. invicta.

Association between Maternal Drug Use and Cytochrome P450 Genetic Polymorphisms and the Risk of Congenital Heart Defects in Offspring

Objective This study aimed to assess the associations between maternal drug use,cytochrome P450(CYP450)genetic polymorphisms,and their interactions with the risk of congenital heart defects(CHDs)in offspring.Methods A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.Results After adjusting for potential confounding factors,the results show that mothers who used ovulatory drugs(adjusted odds ratio[a OR]=2.12;95% confidence interval[CI]:1.08-4.16),antidepressants(a OR=2.56;95%CI:1.36-4.82),antiabortifacients(a OR=1.55;95%CI:1.00-2.40),or traditional Chinese drugs(a OR=1.97;95%CI:1.26-3.09)during pregnancy were at a significantly higher risk of CHDs in offspring.Maternal CYP450 genetic polymorphisms at rs1065852(A/T vs.A/A:OR=1.53,95%CI:1.10-2.14;T/T vs.A/A:OR=1.57,95%CI:1.07-2.31)and rs16947(G/G vs.C/C:OR=3.41,95%CI:1.82-6.39)were also significantly associated with the risk of CHDs in offspring.Additionally,significant interactions were observed between the CYP450 genetic variants and drug use on the development of CHDs.Conclusions In those of Chinese descent,ovulatory drugs,antidepressants,antiabortifacients,and traditional Chinese medicines may be associated with the risk of CHDs in offspring.Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.

Relation of cytochrome P450 2C19 gene 681G>A single nucleotide polynmrphism to clopidogrel resistance after PCI in Chinese

Objectives Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450(CYP) isoenzymes to inhibit platelet aggregation.Individualvariability of platelet inhibition by clopidogrel suggests a possibility for genetic factors having a significant influence on clopidogrel responsiveness.In this study,we sought to determine the association between the single nucleotide polymorphism of CYP 2C19 681G】A and the occurrence of clopidogrel resistance(CR) in Chinese.Methods The study enrolled 614 hospitalized patients who underwentsuccessful percutaneouscoronary intervention with drug-eluting stents were received the treatmentwith dual antiplatelet regimen(aspirin plus clopidogrel).All patients received loading doses of 600 mg clopidogrel and 300 mg aspirin.20μmol/L ADP-induced platelet aggregation ratio(PAR ) was assessed 24 h after clopi- dogrel administration.The maximum residual PAR≥70%was defined as CR.Genomic DNA was extracted from whole blood samples according to standard protocols,the single nucleotide polymorphism of the CYP2C19 681G】A was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all the patients.Results CR was found in 126 patients(20.5%).There was CYP2C19 681G】A polymorphism in the study population.The frequencies of the three kinds of genotypes(GG,GA,A A) in CR group and non-CR (NCR)group were 32.5%,47.6%,19.8%and 48.0%, 45.0%,7.0%,respectively.The frequency of AA genotype was significantly higher in NCR group than that in CR group (OR =3.03,95%CI:1.889～5.784,P=0.003).The A allele carriers were more likely to develop clopidogrel resistance compared with that of G allele carriers(OR=1.85,95%CI: 1.392～2.459,P=0.002).Conclusions CYP2C19 681G/A polymorphism is associated with the risk of CR,and the A allele carriers may be a possible genetic susceptibility factor for patients with CR.

Regulation of P1-450 Gene Expression by Dimethylbenzanthracene in Human Lung Tumor Cells in Culture

Polycyclic aromatic hydrocarbons(PAHs),dimethyl beazanthracene(DMBA)and benzo-(a)-pyrene(BaP),stimulate the expression of the P1-450 gene in human lung tumor cells(ChaGo)in culture.A concentration-and time-dependent increase in the level of P1-450 specific mRNA sequences hasbeen observed in ChaGo cells treated with sublethal concentrations of DMBA.Results presentedsuggest that the parent compound causes the induction of P1-450 gene expression.The methylationpattern of the internal“-C-” residues of the “-CCGG-” sequence has been studied in a stretch ofabout 8000 base pairs(bp)of DNA sequence in and around the P1-450 gene in the control andDMBA-treated ChaGo cells.A comparative Southern blot analysis of the Msp Ⅰ/Hpa Ⅱ digestedDNA of the control and DMBA-treated ChaGo cells followed by hybridization with ^(32)P-labelledregion-specific probes,revealed that i)the internal “-C-” residues of the “-CCGG-” sequences ofdifferent regions of P1-450 gene were methylated to different degrees;ii)DMBA treatment of thecells induced hypomethylation of only the 5' end “-CCGG-” sequences of the gene;and iii)themethylation patterns of “-CCGG-” sequences of most of the coding region and of the 3' end regionof P1-450 gene were not affected by such DMBA treatment.

细胞色素P450酶4F2基因多态性对中国人服用华法林起始七天内剂量的影响

目的:研究细胞色素P450酶4F2(CYP4F2,rs2108622)基因多态性对中国汉族人群服用华法林起始七天内剂量的影响。方法:利用Real-time PCR的方法分析271例服用华法林抗凝患者的CYP4F2基因多态性,记录患者服用华法林七天内的平均华法林初始剂量,国际标准化比值(INR)首次进入治疗窗的时间。统计学方法分析CYP4F2基因多态性的CC,CT和TT各基因型间初始剂量和INR首次进入治疗窗的时间差异。结果:CYP4F2基因多态性的TT、CT/TT基因型的平均华法林初始剂量显著高于CC基因型(P<0.05),差异具有统计学意义。TT基因型的INR首次进入治疗窗的时间显著高于CC基因型(P<0.05),差异具有统计学意义。除外患者性别,年龄,身高,体重,CYP2C9和VKORC1基因多态性以及合并疾病和合用药等多种因素,CYP4F2基因多态性对患者华法林起始七天内华法林剂量的影响仍有统计学意义(回归系数0.21,P=0.003)。结论:在服用华法林的中国人中,CYP4F2基因多态性对华法林起始七天内的剂量有影响。

细胞色素P450 CYP2E1酶构型特征及其表达调控机制的研究进展

细胞色素P450CYP2E1酶参与代谢活化及失活多种前毒物、前致癌物和少数药物。在细胞色素P450超家族中,CYP2E1具有易介导自由基生成引发氧化应激反应的特征。CYP2E1表达水平可能是机体对环境和工业毒物或致癌物敏感程度的重要因素。研究表明,CYP2E1可被多种内、外源性物质所调控,并且CYP2E1的药理和毒理学功能与其以蛋白构型为基础的代谢行为密切相关。本文综述了CYP2E1基因多态性、酶构型特征与其代谢活性间的关系,并分析了其区别于其他细胞色素P450亚型的表达调控机制。

人CYP450 2E1异源性表达模型的建立及底物的表达诱导作用

目的 :探讨化学致癌物二亚硝基哌嗪 (DNP)对人CYP2E1异源表达的诱导作用。方法 :脂质体介导法将外源人CYP2E1cDNA导入NIH 3T3细胞 ,G4 18筛选后挑取克隆 ,Southernblot鉴定外源基因的整合 ,用不同浓度乙醇和DNP处理阳性克隆 ,RT -PCR和Westernblotting检测各组细胞CYP2E1表达水平。结果 :获得二个具有外源基因CYP2E1cDNA整合及稳定表达的细胞克隆 ;随着乙醇和DNP处理浓度的提高 ,细胞CYP2E1mRNA和蛋白质水平的表达增强。结论 :DNP与乙醇能稳定诱导CYP2E1异源表达 ,其作用可能与其mRNA转录增强有关 ;DNP致癌可能与CYP2E1对其原位代谢活化相关。

细胞色素P450 1B1及COMT基因多态性与子宫内膜癌易感性及与mRNA表达关系的研究

目的探讨细胞色素P450 1B1及儿茶酚-O-甲基转移酶(catechol-O-methyltransferase,COMT)基因多态性对子宫内膜癌易感性的影响及与mRNA表达的相关性。方法采用(polymerase chain reaction-restrictionfragment length polymorphism,PCR-RFLP)方法检测122例子宫内膜腺癌患者和114例对照者CYP1B1基因119位、432位密码子和COMT基因158位密码子G→A位点的多态性。对其中36例患者采用反转录-聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)方法检测外周血淋巴细胞中CYP1B1和COMT mRNA的表达。结果 CYP1B1基因119位的突变型(T/T)基因型频率在病例组(8.2%)明显高于对照组(3.5%),432位多态性在病例组与对照组比较差异无统计学意义(P>0.05)。而COMT基因多态在绝经年龄<50岁组,合并杂合型(G/A)和突变型(A/A)与野生型(G/G)比较,病例组与对照组差异有统计学意义(P<0.05,OR=0.422)。野生型(G/G)型COMT mRNA的表达量低于杂合型(G/A)与突变型(A/A)COMT mRNA的表达量,比较差异有统计学意义(P<0.05)。结论 CYP1B1基因119位多态性与子宫内膜癌的发生有潜在的相关性,COMT基因多态与子宫内膜癌的发病风险存在相关性,绝经年龄越早,携带突变等位基因A个体的发病风险减低。所有多态中只有COMT基因第158位密码子多态影响COMT mRNA的表达。

细胞色素P4501A1基因多态性与喉癌遗传易感性的研究

目的 探讨细胞色素P45 0 1A1(cytochromep45 0 1A1,CYP1A1)MspI多态性与喉癌易感性之间的关系。方法 以病例 对照研究 ,采用聚合酶链反应 限制性片段长度多态性分析 (polymerasechainreactionrestrictionfragmentlengthpolymorphism ,PCR RFLP)方法检测 6 2例喉鳞状细胞癌和 5 6例健康对照CYP1A1的基因型 ,并按吸烟指数 (smokingindex ,SI,吸烟支数 /d×吸烟年数 )的不同分析患喉癌风险。结果 CYP1A1MspI分为野生型A、突变杂合型B和突变纯合型C的 3种基因型。杂合型B和突变纯合型C在病例组分别占 5 8 1%和 14 5 % ,对照组分别占 39 3%和 7 1% ,两两比较 ,病例组杂合型B、纯合型C显著高于对照组 ,P <0 0 5 ,比值比率 (oddsration ,OR)分别为 2 89(95 %可信限1 31～ 6 37)和 3 97(95 %可信限 1 10～ 14 2 8)。在低吸烟量组 (SI≤ 40 0 )和高吸烟剂量组 (SI >40 0 )中 ,纯合型C的OR值分别为 4 5 (95 %可信限 0 6 4～ 31 6 1)和 9(95 %可信限 1 6 0～ 5 0 74)。结论 CYP1A1MspI多态性与吸烟协同在喉癌的发生、发展中可能起重要作用。突变纯合型个体患喉癌风险增加 ,吸烟时间越长 ,量越大 。

黄药子及配伍甘草对大鼠肝脏CYP450基因表达的影响

目的:考察甘草对黄药子引起的肝损伤的CYP450酶基因表达的影响。方法:采用逆转录聚合酶链反应(RTPCR)技术检测大鼠肝脏CYP1A2、CYP2C19的mRNA的表达。结果:在mRNA水平上,28天、35天黄药子组均显著诱导CYP1A2的基因表达,配伍甘草后表达降低,具有统计学意义。甘草组可微弱下调CYP2C19的表达,但与配伍组相比无统计学意义。结论:甘草通过抑制CYP1A2的mRNA表达,对黄药子致肝损伤具有一定保护作用。

烟实夜蛾细胞色素P 450 cDNA片段的克隆与序列分析

昆虫细胞色素P 450与昆虫抗药性关系密切,本研究以烟实夜蛾5龄幼虫中肠的总RNA为模板,设计并合成简并引物,利用反转录-多聚酶链式反应(RT-PCR)扩增出了烟实夜蛾细胞色素P 450基因的cDNA片段,将其克隆到pMD 18-T载体进行序列测定,测序得到的491 bp的片断编码163个氨基酸残基,且该片断在阅读框内.与已公布的谷实夜蛾、棉铃虫和烟芽夜蛾细胞色素P 450氨基酸序列进行比较,其一致性分别为98.7%,98.7%和92.1%.

Cytochrome P450 Directed Prodrug Activation Therapy in Research of Cancer Enzymology

Cancer enzymology is a promising filiation of bio-medical sciences. In thepast decades, enzymes, such as GST(glutathione S-transferase) , PKC(protein kinase C) , Topo(DNAtopoisomerases), TK(tyrosine kinase), CD (bacterial cytosine deaminase), CPG2(carboxypeptidase G2) ,and PNP (purine nucleoside phosphorylase), have been known to bear close relations to cancer. Theirspecific expression and influence on the process of tumor initiation, promotion and progressionattract scientists to apply them as a biochemical marker of certain malignant tumor, a predictor ofresponse in cancer chemotherapy; to apply them to drug design, tumor prevention and as adjuvant toradiotherapy or surgery.

PCR和探针自我杂交──Northern Blot方法对二甲基苯蒽诱导的P_（450）Cyp^（1b－1）mRNA的定量

通过ＰＣＲ和探针自我杂交──ＮｏｒｔｈｅｒｎＢｌｏｔ方法对０．３μＭ二甲基苯蒽（ＤＭＢＡ）诱导的２×１０６个小鼠胚胎成纤维细胞１０Ｔ１／２产生的Ｐ４５０Ｃｙｐ１ｂ－１ｍＲＮＡ进行了定量。在这个方法中，与Ｐ４５０Ｃｙｐ１ｂ－１ｍＲＮＡ相同的特定的单链ＣＤＮＡ探针片断通过ＰＣＲ合成。而双链探针中的一条链与单链探针和Ｐ４５０Ｃｙｐ１ｂ－１ｍＲＮＡ的特定片断是相同的。双链探针上的另一条链（Ｈ链）则与单链探针和Ｐ４５０Ｃｙｐ１ｂ－１ｍＲＮＡ的特定片断是互补的。用３２Ｐ－ｄＣＴＰ标记Ｈ链后，它就能够与单链探针和Ｐ４５０Ｃｙｐ１ｂ－１ｍＲＮＡ同时进行杂交。这样，就能用已知浓度的单链探针作为标准物制做标准工作曲线和对Ｐ４５０Ｃｙｐ１ｂ－１ｍＲＮＡ的含量进行定量。经测定，在０．３μＭＤＭＢＡ分别于１、２、３、４、６小时对２×１０６个细胞进行诱导后，２×１０６个细胞在不同时间产生的Ｐ４５０Ｃｙｐ１ｂ－１ｍＲＮＡ分别为０．００９８、０．０１３５、０．０１７４、０．０１９０和０．０１２０μＭ。

细胞色素P450 CYP4A的组织和细胞表达特异性

目的确定细胞色素P450 CYP4A在组织和细胞水平表达是否具有特异性。方法采用Western印迹法分析细胞色素P450 CYP4A蛋白在培养的牛肺动脉内皮细胞、平滑肌细胞及牛肾动脉内皮细胞的表达;采用原位杂交法检测细胞色素P450 CYP4A mRNA在大鼠肺支气管内皮和血管内皮细胞的表达;以14C标记的花生四烯酸(AA)作为反应底物,用荧光高效液相色谱法(HPLC)通过检测牛肺动脉内皮细胞催化外源性AA生成20-羟基廿碳四烯酸(20-HETE)的反应,确定肺动脉内皮细胞是否存在细胞色素P450 CYP4A;将肺动脉内皮细胞破碎并用乙酸乙酯萃取,用荧光物质标记萃取物,用荧光HPLC检测内源性20-HETE,从代谢产物水平确定细胞色素P450 CYP4A的功能蛋白质表达。结果①Western印迹法分析结果表明,细胞色素P450 CYP4A蛋白在牛肺动脉内皮细胞和平滑肌细胞中均有表达,在肺动脉内皮细胞中的表达明显高于平滑肌细胞(积分吸光度值分别为10182±279,5249±167);在牛肾动脉内皮细胞中也有表达,但明显低于肺动脉内皮细胞的表达(积分吸光度值分别为12173±171,17863±207)。②原位杂交结果显示,细胞色素P450 CYP4A mRNA可在大鼠肺支气管内皮细胞和大鼠肺血管内皮均有表达。③用HPLC在牛肺动脉内皮细胞中检测到20-HETE,表明细胞色素P450 CYP4A在肺动脉内皮细胞存在。结论细胞色素P450 CYP4A有其特定的组织和细胞分布,在牛和大鼠肺脏动脉内皮细胞有高表达。

急性脑梗死患者细胞色素P4502D6基因多态性对阿托伐他汀调脂疗效的影响

目的探讨急性脑梗死患者细胞色素P450(CYP)2D6rs1065852位点基因多态性与阿托伐他汀疗效的相关性。方法选择2015年11月~2016年3月我院收治的急性脑梗死患者192例为观察组,另选择同期门诊体检者192例为对照组。检测所有研究对象rs1065852位点基因多态性分布。分析阿托伐他汀治疗3个月后,观察组血脂水平的变化情况。结果观察组高血压、冠心病、饮酒、吸烟及TG水平明显高于对照组(P<0.01),HDL-C水平明显低于对照组[(1.11±0.31)mmol/L vs(1.17±0.35)mmol/L,P=0.049]。2组的等位基因分布及基因型比较无差异,且2组男性携带等位基因A频率与女性比较无差异(P>0.05)。与治疗前比较,阿托伐他汀治疗3个月后观察组GG、GA、AA基因型患者TC、TG及LDL-C水平明显下降,而HDL-C水平明显上升,差异有统计学意义(P<0.05)。治疗3个月后,GG基因型LDL-C水平明显低于GA和AA基因型[(1.05±0.25)mmol/Lvs(1.87±0.45)mmol/L和(1.89±0.12)mmol/L,P<0.01]。结论 CYP2D6rs1065852基因多态性与急性脑梗死患者阿托伐他汀调脂疗效有关,监测该基因多态性有助于预测阿托伐他汀的疗效。

Cytochrome P450 2E1 RsaI/PstI and DraI Polymorphisms Are Risk Factors for Lung Cancer in Mongolian and Han Population in Inner Mongolia

Objective： To explore the relationship between cytochrome P450 2E1 （CYP2E1） RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods： CYP2E1 RsaI/PstI and DraI polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 64 lung cancer patients, 150 healthy Mongolian and 150 healthy Han individuals. The distribution of genotype and allele frequencies of CYP2E1 RsaI/PstI and DraI polymorphisms were studied. Results： The risk of lung cancer was increased in individuals with CYP2E1 （cl/cl） and CYP2E1 （DD） with OR values of 2.431 （95%CI=1.082-5.460） and 2.778 （95%CI=1.358-5.683） respectively （P0.05）. When CYP2E1 RsaI/PstI and DraI polymorphisms were combined, the risk of lung cancer was reduced in individuals with CYP2E1 （cl/c2＋c2/c2 and DD＋CC） with OR values of 0.233 （95%CI=0.088-0.615, P0.05）. In smokers, the susceptibility to lung cancer was higher in the individuals with CYP2E1 （c1/c1） and CYP2E1 （DD） than in the individuals with c2 and C allele （P0.05, OR=2.643 and 4.308 respectively）. There was no significant difference in distribution of CYP2E1 genotype frequency between healthy Mongolian, Han population and lung cancer patients, healthy controls in Inner Mongolia. Conclusion： CYP2E1 （c1/c1） and CYP2E1 （DD） are predisposing factors of lung cancer in population in Inner Mongolia. CYP2E1 （c2﹢C） co-mutation may decrease the risk of lung cancer. Smoking exerts synergetic effect with CYP2E1 （c1/c1） and CYP2E1 （DD） on the occurrence of lung cancer.

Response of Cytochrome P450 Expression to Maize Volatiles in Helicoverpa armigera (Hner)

The 7-ethoxycoumarin O-deethylase （ECOD） activities of cytochrome P450s and differential expression of six cytochrome P450 genes induced by the volatiles from both damaged and undamaged maize plants were investigated in the cotton bollworm, Helicoverpa armigera （Hiabner）. The ECOD activity changed with time of exposure to maize volatiles. At 36 h after cotton bollworm larvae exposure to maize volatiles, the ECOD activities in cotton bollworm damaged and artificially damaged groups were 2.36 and 4.53 times higher than the control group respectively. The relative expression levels of CYP4S1, CYP6B2 and CYP6B7 in the cotton bollworm were significantly increased in artificially damaged plant group, which was 2.93, 5.09 and 10.66 times higher than that in the control group, respectively. The expression levels of CYP6B2, CYP6B6, CYP9A12, and CYP9A14 were much lower in the larvae exposure to volatiles from both healthy and pest damaged maize seedlings than in the control group at 12 h after larvae exposure to maize volatiles. For the cotton bollworm damaged maize group, the expression of CYP4S1 and CYP9A14 increased.

The effects of CYP1A1 gene polymorphism and p16 gene methylation on the risk of lung cancer in a Chinese population

Objective： To investigate the relationship between the genetic polymorphism of CYP1A1 and the genetic susceptibility to lung cancer as well as to study the effects of the methyiation in p16 gene on the risk of lung cancer in a Chinese population. Methods： A case control study was conducted among 47 cases of lung cancer and 94 controls. The genetic polymorphism of CYP1A1 was tested with method of PCR-RFLP, and a methylation-specific PCR （MSP） was performed to detect p16 methylation. Results： It showed that there was no significant difference in frequencies of the genotypes of CYP1A1 between the two groups （P 〉 0.05）. Synergistic effects were not found between smoking and CYP1AI. Methylated p16 gene was found in 44.7% （21/47） of lung cancer tissues and in 17.0% （8/47） of normal lung tissues with significant difference （P 〈 0.05）. Conclusion： The genetic polymorphism of CYP1A1 does not increase the risk of lung cancer in a Chinese population. The methylation in p16 gene may be the most common mechanism to inactivate p16 gene in lung cancer, and is not significantly associated with genotype of CYP1A1,