MCM7基因启动子区-153A〉T多态位点对宫颈癌遗传易感性及基因转录活性的影响

目的：探讨MCM7基因启动子区-153A〉T多态位点（rs1534310）与宫颈癌遗传易感性的关系及对基因转录活性的影响。方法：利用聚合酶链式反应一限制性片段长度多态性（PCR—RFLP）分析技术，对87例宫颈癌患者和116名健康对照的MCM7—153A〉T多态位点进行分型，采用非条件逻辑回归分析统计该多态位点与宫颈癌易感性的相关性。构建含-153A〉T多态位点所在启动子区的双荧光报告载体，分析MCM7基因启动子区-153A〉T多态位点对基因转录活性的影响。结果：TT、AT、AA基因型在病例组中的频率分别为23．O％、46．O％和31．O％，在对照组中分别是27．6％、44．0％和28．4％，两组间基因型频率分布差异无统计学意义（P=0．753）。非条件逻辑回归分析发现，以TT基因型作为参照，AT和AA基因型均没有显著增加个体患宫颈癌的风险（OR=1．26，95％CI=0．63—2．52，P=0．522以及OR=0．54，95％CI=0．62—2．79，P=0．485）。双荧光素酶报告基因分析结果显示含有-153A或T等位基因的启动子转录活性没有显著性差异（P=0．825）。结论：MCM7—153A〉T多态位点不影响基冈转录的活性，并且与广东汉族妇女宫颈癌易感性无相关性。     

MMP-12和MMP-13基因启动子区功能性多态与喉癌遗传易感相关性研究

目的：探讨基质金属蛋白酶-12（matrix metaIIoproteinases-12,MMP-12）基因启动子区-82A／G和MMP-13基因启动子区-77A／G基因多态（single nucleotide polymorphism,SNP）与中国北方汉族人群喉鳞状细胞癌（1aryngeal squa—mous cell carcinoma,LSCC）发病易感性的相关性。方法：采用聚合酶链式反应-连接酶检测反应（PCR—LDR）技术检测148例LSCC患者和148例健康对照个体MMP-12—82A／G多态（rs2276109）、MMP-13-77A／G多态（rs2252070）的基因型。结果：患者组中MMP-12—82A／G多态的A、G等位基因频率（98．6％、1．4％）与对照组（93．6％、6．4％）相比差异有统计学意义,P=0．001;基因型频率分布与对照组相比差异有统计学意义,P=0．001;与A／A基因型相比,A／G基因型可显著增加喉鳞状细胞癌的发病风险,0R=5．30,95％CI：1．76～16．00。MMP-13—77A／G多态的A、G等位基因频率在患者组中为42．2％和57．8％,与对照组的32．4％和67．6％相比差异有统计学意义,P=0．01;但基因型频率分布与对照组相比差异无统计学意义,P=0．07。进一步分析发现,该遗传模型为显性遗传。结论：MMP-12—82A／G多态、MMP-13—77A／G多态与LSCC发病风险有关,-82G与-77A等位基因可能成为预测中国北方汉族人群喉鳞状细胞癌发病风险的独立危险因素。     

CYP1A1和GSTM1基因多态性与内蒙古人群肺癌易感性的关系

背景与目的 肺癌是严重危害人类健康的恶性肿瘤之一，其发病与肺癌人群中某些肺癌相关基因的遗传多态性有关。本研究旨在探讨细胞色素P4501A1（CYP1A1）基因多态性和谷胱甘肽硫转移酶M1（GSTM1）基因多态性与内蒙古人群肺癌易感性的关系。方法 用PCR-RFLP技术分析了原发性肺癌组和住院对照组（各163例）的CYP1A1、GSTM1基因的多态性、基因型分布频率和交互作用。结果 CYP1A1突变型和GSTM1基因缺陷型EGSTM1（-）]频率分布分别为36．8％、65．0％（病例组）和19．0％、48．9％（对照组），二者经χ^2检验差异有显著性（χ^2=12．82，P=0．000；χ^2=9．78，P=0．002）。CYP1A1突变型患肺癌的风险显著增加（OR=2．48，95％CI为1．51～4．08）。GSTM1（-）者患肺癌的风险也显著增加（OR=2．03，95％CI为1．30～3．17）。基因突变的协同分析发现CYP1A1突变型／GSTM1（-）在肺癌组和对照组中的分布频率分别为28．8％和8．0％，二者经χ^2检验有显著性差异（χ^2=23．883，P=0．000）。CYP1A1突变型／GSTM1（-）患肺癌的风险显著增加（OR=4．90，95％CI为2．50～9．83）。无论是在肺癌组还是在对照组，CYP1A1突变型／GSTM1（-）和CYP1A1非突变型／GSTM1（-）在性别间分布频率的差异均无显著性（肺癌组χ^2=0．797，P=0．372；对照组χ^2=0．670，P=0．761）。吸烟与肺癌易感性的统计学分析，结果显示吸烟与肺癌易感性有关（χ^2=14．197，P=0．000），吸烟者患肺癌的风险显著增加（OR=2．33，95％CI为1.50～3．62）。CYP1A1突变型与吸烟关系的协同分析发现，携带CYP1A1突变型基因的吸烟者较携带CYP1A1突变型基因不吸烟者易患肺癌（OR=4．44，95％CI为2．40～8．32，χ^2=23．843，P=0．000）。GSTM1（-）与吸烟关系的协同分析中也发现，携带GSTM1（-）的吸烟者患肺癌的风险显著增加（OR=7．32，95％CI为3．39～15．50，χ^2=36．708，P=0．000）。结论 CYP1A1突变型和GSTM1（-）是内蒙古地区肺癌的易患因素，二者对肺癌的发生有协同作用，吸烟与肺癌的易感性也有关，CYP1A1突变型、GSTM1（-）与吸烟在肺癌的发生上也有相互促进作用。     

微粒体环氧化物水解酶EPHX1基因多态性与肝细胞性肝癌易感性的Meta分析

目的探讨微粒体环氧化物水解酶编码基因EPHX1多态性与肝细胞性肝癌（HCC）遗传易感性的关系。方法按照制定的检索策略,枪索相关数据库中的文献,获取有关EPHX1基因多态性与HCC易感性的病例一对照研究,提取相关数据进行Meta分析。以病例组和对照组基因型分布的比值比（OR）为效应指标,对纳入文献进行异质性检验,应用Statal2．0软件以不同合并模型对各研究原始数据进行Meta合并,计算合并效应量OR值及其95％可信f）（间（CI）。结果共纳入9篇文献,EPHX1337T〉C多态位点的共8个研究,累计病例584例,对照989例。等位基因比较模型（CYST）的OR值为1．47（95％CI=1．26～1．72,P〈0．001）;纯合子比较模型（CC vs TT）的OR值为1．88（95％CI=1．40～2．52,P〈0．001）;隐性模型（CCV vs CT/TT）的OR值为1．73（95％CI=1．36～2．21,P〈0．001）。EPHX1416A〉G多态位点共6项研究,累计病例432例,对照699例。等位基因比较模型（GVSA）的OR值为0．75（95％CI：0．59～0．95,P=0．018）。结论EPHX1337T〉C多态位点CC基因型与HCC易感性升高有关;416A〉G多态位点等位基凶G可能降低HCC易感性,为保护基因型。     

XRCC2基因多态性与肺癌易感性关系的研究

目的：探讨中国北方人群中XRCC2基因C41657T、G4234C多态性与肺癌的关系。方法：应用PCR-RFLP方法检测199例肺癌患者和200例正常人的XRCC2 C41657T及G4234C多态位点，比较两组之间等位基因及基因型频率分布及其与肺癌的关系。结果：肺癌患者XRCC2 C41657T多态位点的CC、CT、TT基因型和C、T等位基因频率分布与健康对照组相比差异均无统计学意义（P〉0．05）。G4234C多态位点的GG、GC、CC基因型和G、C等位基因频率分布与健康对照组相比差异也均无统计学意义（P〉0．05）。两多态性位点联合分析显示，肺癌患者与健康对照组的4个单体型分布亦无统计学差异（P〉0．05）。以病理类型、吸烟状况和年龄进行分层分析显示，XRCC2 C41657T多态位点可能与腺鳞癌和不吸烟人群的肺癌发病风险相关；与C／C基因型相比，携带T等位基因的基因型（C／T＋T／T）可显著增加腺鳞癌的发病风险（OR为2．95，95％CI=1．15—7．59）；而C／T基因型可显著增加不吸烟组人群中肺癌的发病风险（OR为2．12，95％CI=1．05-4．27）。对于XRCC2 G4234C多态位点，与G／G基因型相比，G／C基因型和携带C等位基因的基因型（G／C＋C／C）可显著增加小细胞肺癌的发病风险（OR为2．82和2．82；95％CI=1．15～6．91和1．17～6．76）；G／C基因型或与C／C基因型相加可显著增加年龄≥60岁的人群中肺癌的发病风险（OR为2．29和2．37；95％CI=1．11—4．72和1．16—4．88）。结论：对于XRCC2 C41657T多态位点，携带T等位基因的基因型可能增加腺鳞癌的发病风险，C／T基因型可能增加不吸烟者患肺癌风险；XRCC2 G4234C多态位点，G／C基因型或携带C等位基因可能增加小细胞肺癌的发病风险和老年人（年龄≥60岁）患肺癌的风险。     

XPD基因多态性与非吸烟女性肺癌易感性的关系

背景与目的 着色性干皮病互补基因D（xeroderma pigmentosum group D，XPD）是一种重要的DNA损伤修复基因，其常见的多态是位于751密码子的A→C多态。本研究旨在探讨XPD基因751位点单核苷酸多态性与非吸烟女性肺癌易感性的关系，并探讨油烟暴露与基因多态性交互作用对肺癌风险的影响。方法 采用病例-对照研究方法，纳入非吸烟女性肺癌患者105人和对照105人。以聚合酶链反应-限制性片段长度多态性方法分析XPD基因Lys751Gln多态基因型。结果 携带至少1个751Gln等位基因者患肺癌的风险显著增高，调整OR为2．80（95％CI为1．21～6．48）。携带等位基因751Gln又有油烟暴露的个体患肺癌的风险较两个危险因素单独作用时更高，校正OR为6．85（95％CI为1．69～27．67，P=0．007）。结论 XPD基因Lys751Gln多态是非吸烟女性肺癌的遗传易感因素。携带XPD751Gln等位基因又有油烟暴露的非吸烟女性患肺癌的风险明显增高。     

叶酸还原载体基因RFC1 G80A多态性与胃癌易感性关系的分子流行病学研究

目的：探讨中国华东汉族人群叶酸还原载体（reduced folate carrier，RFC1）基因G80A多态与胃癌易感性的关系。方法：本组为病例对照研究，经组织学确诊的宜兴高发区胃腺癌病例261例，并选择与病例年龄和性别频数匹配的人群对照295例，以PCR内切酶片段长度多态性方法，比较不同基因型与胃癌风险的关系，并探讨吸烟、饮酒等因素在其中的影响。结果：与携带80GG基因型者比较，携带80AA基因型者胃癌风险增加1．79倍（校正OR=2．79，95％CI：1．77～4．39）；以携带80GG和GA基因型者为参照（隐性模型），80AA变异基因型者胃癌风险增加1．59倍（校正OR=2．59，95％CI：1．77～3．80），且这一显著的相关性在60岁以上（校正OR=2．96，95％CI：1．63～5．37）、女性（校正OR=8．28，95％CI：2．95～23．26）、非吸烟者（校正OR=3．68，95％CI：1．94～6．98）和非饮酒者（校正OR=3．08，95％CI：1．76～5．41）中更为显著。结论：RFC1G80A多态可能与中国汉族人群胃癌遗传易感性有关，值得进一步进行功能学探讨及大样本人群验证。     

南京市人群NQO1、CYP1A1、mEH基因多态性与肺癌易感性研究

目的：探讨南京市人群人NQO1，CYP1SA1，mEH-exon3,mEH-exon4基因多态性与肺癌易感性的关系。方法：用病例－对照研究方法，收集南京市区原发性肺癌患者84例，其中鳞癌35例，腺癌49例，同时选择对照84例，采用PCR技术，对样本NDA进行NQO1，CYP1A1，mEH-exon3,mEH-exon4基因的检测，并分析各基因型与肺癌易感性的关系。结果：南京市区人群NQO1，CYP1A1和mEH-exon4与肺癌易感性没有明显关系。mEH-exon3基因型与肺鳞癌发生有关，野生型个体可降低肺鳞癌发病的风险（OR＝0．32，95％CI：0．0078－0．63），杂合型和突变型个体患肺鳞癌的危险性明显高于野生型个体（OR＝3．1，95％CI：0．08－6．12），考虑吸烟因素后，mEH-exon3基因型与吸烟者肺癌发生有关，野生型个体可使肺癌发病风险性降低（OR＝0．18，95％CI：0．06－0．29），杂合型和突变型个体患肺癌的危险性增高（OR＝5．66，95％CI：2．01－9．30）。结论：南京市人群中NQO1，CYP1A1，mEH基因的分布情况与国内外的相关报道存在一定差异；种族差异，地域不同可能是造成上述基因分布不同的重要原因，南京市人群中mEH-exon3基因杂合型和变型与肺鳞癌发生有关，与吸烟者肺癌发生关系更为密切。     

GSTT1基因多态性与中国四川汉族人群肺癌遗传易感性关系的研究

背景与目的GSTs可能参与机体致癌物的解毒反应，如保护个体免受吸烟的损害，因此GSTs基因多态性被认为是个体是否患癌的易感因素。本研究的目的是探讨GSTT1基因多念性与中国四川汉族人群肺癌遗传易感性的关系。方法采用病例对照和PCR—RFLP方法检测中国四川汉族人群肺癌患者150例和健康对照者152例的GSTT1基因缺失型的频率，并评价其与吸烟和肺癌遗传易感性的关系。结果①GSTT1（-）基因型在肺癌组和对照组分别为54．7％(82／150)和38．2％(58/152)．二者间比较有显著性差异(OR=1．681，95％CI=1，009～2．803，P=0．046)；②GSTT1(-)基因型患肺鳞癌(OR=2．969．95％CI=1．511～5．834。P=0．002)及肺腺癌(OR=2．095．95％CI=1．060～4．140，P=0．033)的风险性明显增加；③吸烟者中GSTT1(-)基因型者患肺癌的风险是GSTT1( )者的4．051倍；①GSTT1(-)基因型者中，吸烟者患肺癌的风险是不吸烟者的53．885倍；⑤吸烟≥20包年者中，GSTT1(-)基因型者患肺癌的风险是GSTT1( )者的4．296倍。结论①(GSTT1(-)基因型增加四川汉族人群患肺癌的风险性．特别是增加患肺鳞癌的风险；②GSTT1(-)基因型和吸烟之间存在交互作用，吸烟量越大且为GSTT1(-)基因型者则患肺癌的风险性越大。     

亚甲基四氢叶酸还原酶A1298C基因多态性与肝细胞性肝癌遗传易感性的Meta分析

目的探讨亚甲基四氢叶酸还原酶（methylenetetrahy drofolate reductase,MTHFR）A1298C基因多态性与肝细胞性肝癌（hepatocellular carcinoma,HCC）遗传易感性的关系。方法计算机检索PubMed、EMbase和中国学术期刊全文数据库等,收集有关MTHFR基因多态性与HCC遗传易感性的病例一对照研究资料,按照纳入标准选择文献,提取相关数据进行Mcta分析。以病例组和对照组基凶型分布的比值比（OR）为效应指标,对纳入文献进行异质性检验,应用Stata12．0软件对各研究原始数据进行Meta合并,计算合并效应量OR值及95％可信区间（95％CI）。结果共纳入6项病例一对照研究,病例组为1708例,对照组为2911名。等位基因比较模型（C vs A）：OR（95％CI）=0．95（0．85～1．06）,P=0．342;纯合子比较模型（CC vs AA）：OR（95％CI）=0．55（0．38～0．79）,P=0．001;隐性模型（CC vs AC／AA）：OR（95％CI）=0．54（0．38～0．78）,P=0．001。结论MTHFR A1298C基因多态位点CC基因型能够降低HCC遗传易感性,为保护基因型。     

Eradication of Helicobacter pylori Restores Glutathione S-Transferase Activity and Glutathione Levels in Antral Mucosa

Glutathione S-transferases (GST) and glutathione peroxidases (GPO) are important in detoxification. GST activity in the mucosa of the gastrointestinal tract is inversely correlated with the development of gastrointestinal cancer. Helicobacter pylori (H. pylori) infection has been associated with gastric cancer. We studied GST activity and the substrate glutathione (GSH) in patients with H. pylori-associated gastritis. GST activity and isoenzyme levels, GPO activity and GSH levels were studied in antral biopsies of 38 H. /pyfori-positive patients, before and after eradication treatment. In 31 patients in whom H. pylori was successfully eradicated, antral GST enzyme activity before therapy was 532 (465–598) nmol/mg protein-min (mean and 95% confidence interval) and that after therapy was 759 (682–836) nmol/mg protein-min ( P <0.0001). Correspondingly, levels of GST α and GST-P1 were higher after eradication ( P <0.001). GSH concentration significantly increased: 21.2 (16.2–26.2) nmol/mg protein before and 27.1 (23.6–30.6) nmol/mg protein after therapy ( P <0.05). In 7 patients in whom H. pylori was not eradicated, GST activity was 671 (520–823) nmol/mg protein min and 599 (348–850) nmol/mg protein before and after treatment respectively ( P =0.32). GSH levels were 17.4 (9.0–25.7) nmol/mg protein and 18.2 (9.1–27.3) nmol/mg protein, respectively ( P =0.84). No differences in antral GPO enzyme activity, both of selenium (Se)-dependent and total GPO, before and after successful treatment were found. Eradication of H. pylori infection increases GST activity and GSH levels in antral mucosa. Low GST activity and GSH concentration due to H. pylori infection might play a role in gastric carcinogenesis.     

Activity of melphalan in combination with the glutathione transferase inhibitor sulfasalazine

Glutathione (GSH) transferases (GST), a family of detoxification enzyme proteins, are suggested to play an important role in tumor cell resistance to melphalan. The GST-activity inhibitor ethacrynic acid has been shown to increase the antitumor activity of melphaln in vitro as well as in vivo. In this study we determined the activity and toxicity of melphalan in combination with another GST-activity inhibitor, sulfasalazine, an agent used to treat ulcerative colitis. We entered 37 previously treated patients with advanced cancer of different histologies on sulfasalazine given at the individually calculated maximum tolerated dose (MTD) and melphalan given at doses beginning at 20 mg/m². The main toxicity arising from this combination was nausea and vomiting, whereas increased myelosuppression was not observed. A partial response was seen in 2/4 of the ovarian cancer patients only. Plasma sulfasalazine levels varied between 2.5 and 47.1 g/ml. Although reductions in GSH/GST levels were observed in peripheral mononuclear cells of certain patients following sulfasalazine treatment, there was no correlation between the extent of reduction and the plasma sulfasalazine level. A larger patient population must be studied to determine the usefulness of this combination.This investigation was supported in part by a grant from the Pittsburgh Mercy Foundation and by USPHS grant CA 50638, awarded by the National Cancer institute     

Low Glutathione and Glutathione S-Transferase Levels in Barrett's Esophagus as Compared to Normal Esophageal Epithelium

Patients with Barrett's esophagus, wherein squamous epithelium has been replaced by columnar epithelium, have an increased risk for developing esophageal adenocarcinoma as compared to the general population. Glutathione S-transferase (GST), a family of detoxification enzymes consisting of class α, μ, π, and θ isoforms, is involved in detoxification of carcinogens and low levels of these enzymes correlated with high cancer risk. We have now compared GST enzyme activity, GST isoenzyme composition and glutathione (GSH) content of Barrett's mucosa with that of adjacent normal squamous epithelium. Biopsy specimens of 98 patients with Barrett's esophagus were taken from both Barrett's and adjacent normal squamous epithelium. GST enzyme activity towards 1–chloro-2,4–dinitrobenzene was measured, and GST isoenzyme levels were determined by densitometrical analyses of western blots after immunodetection with monoclonal antibodies. Total GSH content was determined by high-performance liquid chromatography after conjugation with monobromobimane. Wilcoxon's signed rank test and Spearman correlation analyses were used for statistical evaluation. As compared with adjacent normal squamous epithelium, GST enzyme activity in Barrett's epithelium was reduced by 35%, and GST μ, GST π and GSH levels were reduced by 24%, 30%, and 63%, respectively. However, the minor GST α and GST θ levels were higher in Barrett's epithelium (by 625% and 33%, respectively). High levels of GSH and GSTs in general are correlated with protection against cellular or cytogenetic damage. The observed reduction in GSTs and GSH in Barrett's epithelium may therefore contribute to the increased cancer risk in this tissue.     

Glutathione S-Transferases in Small Intestinal Mucosa of Patients with Coeliac Disease

Patients with villous atrophy due to coeliac disease have an increased risk of developing small intestinal malignancies. Intestinal glutathione (GSH) and glutathione S‐transferases (GST) are involved in the protection against carcinogenesis. The aim of this study was to evaluate GSH content and GST enzyme activity in small intestinal mucosa of untreated coeliacs compared to controls. We evaluated GSH content and GST enzyme activity, including the levels of GST classes α, μ, π, θ in small intestinal biopsies of untreated coeliacs (flat mucosa, Marsh IHC, n=12) compared to normal subjects (n=23). Next, we evaluated GSH and GST's in coeliacs in remission (Marsh 0‐1, n=11), coeliacs with persisting villous atrophy while on a gluten‐free diet (partial villous atrophy, Marsh IIIA (n=5); subtotal villous atrophy, Marsh IIIB (n=6) and patients with infiltrative/crypt‐hyperplastic Marsh II lesions (n=4). Total GST enzyme activity and content of GSTa are markedly suppressed in Marsh IIIC lesions compared to controls (resp. 220±79 vs. 4641189 nmol/mg protein‐min (P<0.001) and 2.79±2.46 vs. 6.47±2.29 μg/mg protein (P<0.001). In coeliacs in remission these levels normalized. Total GST enzyme activity and GSTα levels are proportionately lowered according to the degree of mucosal pathology in Marsh II, IIIA and IIIB. (Spearman's σ correlation coefficient for total GST, ‐0.596, P<0.001; GSTα, ‐0.620, P<0.001). GSTμ, π and θ and GSH levels are not significantly different in the selected study groups of mucosal pathology compared to controls. Total GST enzyme activity and content of GSTα in small intestinal mucosa are significantly lower in untreated coeliac disease compared to controls. In Marsh II, IIIA and IIIB, GST enzyme activity and GSTα content are proportionally lower according to the degree of mucosal pathology. Normal values are seen in coeliacs in remission. This correlation between coeliac disease and a suppressed GSH/GST detoxification system may explain in part the carcinogenic risk in untreated coeliac disease.     

Granulocyte-colony stimulating factor enhances anti-tumour effect of hyperthermia

The combined effect of granulocyte-colony stimulating factor (GCSF) and hyperthermia in the treatment of experimental tumours was studied to examine the possible involvement of activated granulocytes in the antitumour effect of hyperthermia. Two weeks after transplantation of SCC VII cells (1 x 105) into the instep of the left leg of C3H/HeJ male mice, the mice were given subcutaneous injections of GCSF (0.2mg/kg) for 4 days. On day 4, hyperthermia was applied locally at 43 C for 40min. Hyperthermia inhibited the tumour growth, and this effect was enhanced by pre-treating the animals with GCSF. The numbers of circulating neutrophils in control and GCSF-treated mice were 2728 +/- 517/mul and 3124 +/- 194/mul, respectively ( p = 0.53). Hyperthermia increased the number of neutrophils to 4409 +/- 700/mul ( p &lt; 0.05). Hyperthermia combined with GCSF significantly increased the number of netrophils to 5479 +/- 691/mul ( p &lt; 0.01). Chemiluminescence analysis using L-012 revealed that GCSF enhanced the generation of reactive oxygen species by about 10-fold. Glutathione contents in tumours 24h after hyperthermia decreased by about 50% in both the hyperthermia groups with or without GCSF, as compared to those in the control. The GCSF-enhanced anti-tumour activity of hyperthermia was markedly inhibited by administration of a long-acting superoxide dismutase derivative (SM-SOD). These results suggest that GCSF activates the ability to generate active oxygen species by neutrophils and, thereby, enhances the anti-tumour effect of hyperthermia.     

贝叶多孔菌水相提取液对大鼠肝脏谷胱甘肽硫转移酶、还原型谷胱甘肽和细胞色素P450的影响

贝叶多孔菌（Ｐｏｌｙｐｏｒｕｓｆｒｏｎｄｏｓｕｓ，Ｐｆ）是属于担子菌亚门多孔菌属的食用菌，其提取液有抑突变作用，本文旨在探讨其作用机理，现将其对大鼠肝脏谷胱甘肽硫转移酶活性、还原住谷胱甘肽水平和细胞色素Ｐ４５０含量影响的研究报道如下：Ｗｉｓｔａｒ大鼠２４只，雌雄各半，随机分为２组，灌胃分别给予蒸馏水和加热的１４．２８％Ｐｆ水相是取液１０ｍｌ／ｋｇ，每日两次，连续１０ｄ，然后剖验，该液对大鼠肝脏ＧＳＴ活性，ＧＳＨ水平和Ｐ４５０含量均有一定的提高作用，增长率分别为２７．５０％，４７．５０％和３３．３３％。这可能是Ｐｆ抑诱变作用的机理之一。     

血液肿瘤细胞对氧化砷的敏感性与其抗氧化能力的关系

目的　探讨血液肿瘤细胞对三氧化二砷 (As2 O3 )的敏感性和细胞抗氧化能力的关系。方法　应用 9个血液肿瘤细胞系 ,通过细胞活力、形态学和流式细胞仪检测细胞凋亡 ,并测定细胞系的谷胱甘肽 (GSH)含量和 4种抗氧化酶的活性。结果　除了HL 6 0、U937、K5 6 2和Jurkat细胞外 ,其他5个细胞对As2 O3 诱导的凋亡敏感。与敏感细胞系比较 ,As2 O3 耐受细胞系存在较高的GSH含量和(或 )过氧化氢酶活性。谷胱甘肽过氧化物酶、谷胱甘肽S转移酶和超氧化物歧化酶活性与细胞对As2 O3 诱导凋亡效应敏感性无明显相关。结论　细胞内GSH水平和过氧化氢酶的活性是决定血液肿瘤细胞对As2 O3 敏感性的重要因素。     

Association of Glutathione-S-Transferases M1 and T1 Deletional Variants with Development of Oral Squamous Cell Carcinoma: A Study in the South-East of Iran

Background: The role of genetic polymorphisms in genes of Glutathione-S-transferases (GST) enzymes in susceptibilityto oral cavity cancers is controversial. Oral Squamous Cell Carcinoma (OSCC) is the most common oral cavity neoplasm.Aimed to evaluate the potential impacts of two well-known null variants residing in the gene encoding GSTM1 andGSTT1 enzymes of OSCC patients in the southeast of Iran. Methods: In a case-control design, 113 individuals (50OSCC patients, and 63 healthy subjects) were included. DNA was extracted using paraffin-embedded tissues. GSTgenotyping was carried out using multiplex PCR. Results: In 113 participants, 41 (36.3%) and 72 (63.7%) were malesand females respectively. No significant difference was recognized for distribution of GSTM1 (P=0.11) and GSTT1(P=0.28) null genotypes between OSCC patients (58%, and 24% respectively) and healthy controls (42.9% and 15.9%respectively). Also, no significant difference was noted regarding the frequency of GSTM1 null genotype in differenthistological grades, however, those patients with more aggressive disease (poorly differentiated or grade III) revealedwith a significantly higher ratio (66.7%) of GSTT1 null genotype (P=0.002). The highest odds ratio for OSCC was relatedto combined null genotypes for GSTM1 and GSTT1 (OR=2.5, 95% CI: 0.7-9.2), however, this was not statisticallysignificant finding (P=0.15). Conclusion: Null genotypes polymorphisms were more common in OSCC than healthyindividuals. GSTT1 null genotype may be an important genetic factor in the progression of OSCC.     

Role of ferroptosis in colorectal cancer

Colorectal cancer(CRC) is the second deadliest cancer and the third-most common malignancy in the world. Surgery, chemotherapy, and targeted therapy have been widely used to treat CRC, but some patients still develop resistance to these treatments. Ferroptosis is a novel non-apoptotic form of cell death. It is an iron-dependent non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species and has been suggested to play a role in reversing resistance to anticancer dr...     

Potential Chemoprevention Activity of Pterostilbene by Enhancing the Detoxifying Enzymes in the HT-29 Cell Line

Detoxifying enzymes are present in most epithelial cells of the human gastrointestinal tract where they protectagainst xenobiotics which may cause cancer. Induction of examples such as glutathione S-transferase (GST)and its thiol conjugate, glutathione (GSH) as well as NAD(P)H: quinoneoxidoreductase (NQO1) facilitate theexcretion of carcinogens and thus preventing colon carcinogenesis. Pterostilbene, an analogue of resveratrol, hasdemonstrated numerous pharmacological activities linked with chemoprevention. This study was conducted toinvestigate the potential of pterostilbene as a chemopreventive agent using the HT-29 colon cancer cell line tostudy the modulation of GST and NQO1 activities as well as the GSH level. Initially, our group, established theoptimum dose of 24 hours pterostilbene treatment using MTT assays. Then, effects of pterostilbene (0-50 μM)on GST and NQO1 activity and GSH levels were determined using GST, NQO1 and Ellman assays, respectively.MTT assay of pterostilbene (0-100 μM) showed no cytotoxicity toward the HT-29 cell line. Treatment increasedGST activity in the cell line significantly (p<0.05) at 12.5 and 25.0 μM. In addition, treatment at 50 μM increasedthe GSH level significantly (p<0.05). Pterostilbene also enhanced NQO1 activity significantly (p<0.05) at 12.5μM and 50 μM. Hence, pterostilbene is a potential chemopreventive agent capable of modulation of detoxifiyingenzyme levels in HT-29 cells.