细胞色素P450与肺癌关系的研究进展

细胞色素P450(CYP450)属血红蛋白类酶,是微粒体混合功能氧化酶系中最重要的一族氧化酶,分布在生物体内的各种器官组织,其作用底物非常广泛,参与机体内大部分外源性、内源性致癌物质以及抗癌药物的代谢。不同的CYP450分别代谢不同的致癌物质以及抗癌药物。现已证实CYP450家族中许多酶都具有基因多态性,其多态性在人群中的分布与多种肿瘤的易感性以及抗肿瘤药物的代谢密切相关。     

细胞色素P450基因多态性与肿瘤关系研究进展

毒物代谢酶基因多态是肿瘤易感性的一个重要方面。本就细胞色素Ｐ４５０同工酶中的ＣＹＰ１Ａ１、ＣＹＰ２Ｄ６和ＣＹＰ２Ｅ１的基因多态及其与肿瘤易感性的关系作一介绍。     

昆虫细胞色素P450异源表达

细胞色素P450酶在昆虫生长、发育及代谢外源化合物上起重要作甩，异源表达是研究昆虫P450酶的结构、功能及其表达调控的重要途径。昆虫细胞色素P450异源表达主要有三大体系：细菌、酵母、杆状病毒表达系统，本就上述三太表达体系在昆虫细胞色素P450研究中的应用作一综述。     

细胞色素P450与肿瘤的基因治疗

利用细胞色素P450治疗肿瘤是一种新的基因治疗方法,对提高肿瘤化疗的安全性和有效性有非常大的潜力。这种方法的首要目标就是选择性地使细胞色素P450在肿瘤细胞内超量表达。P450酶系降解的前药大部分在肿瘤内活化,提高了肿瘤细胞内药物的相对浓度,减小药物对其它组织的细胞毒性。本文概述了可被细胞色素P450降解的用于肿瘤治疗的前药以及重组细胞色素P450在基因治疗中的应用。     

细胞色素P450酶与肿瘤的遗传易感性

细胞色素Ｐ４５０酶主要参与外来化合物进入体内后的第一阶段激活反应。Ｐ４５０酶具有催化特异性,同种Ｐ４５０酶在人群中可以表现为不同表型,这种遗传多态现象决定Ｐ４５０酶对特定的外来化合物在反应上的各异,即表现为个体对环境致癌性的不同易感性。     

广州地区汉族人群细胞色素P450 1A1和细胞色素P450 2E1基因多态性

目的 探讨广州地区汉族人群细胞色素Ｐ４５０ １Ａ１（ＣＹＰ１Ａ１）和细胞色素Ｐ４５０ ２Ｅ１（ＣＹＰ２Ｅ１）基因的多态性分布规律。方法 用ＰＣＲ－ＲＦＬＰ和等位基因特异性扩增技术,对１５０名广州地区汉族正常人的ＣＹＰ１Ａ１和ＣＹＰ２Ｅ１基因多态性进行了检测,并与其他人群进行了比较。结果 ＣＹＰ１Ａ１基因３’端非翻译区的Ｍｓｐ１多态位点ｍ１（ＭＳＰⅠ－）、ｍ２（ＭｓｐⅠ＋）等位基因频率分别为６２．３     

细胞色素P450酶与肿瘤的遗传易感性

细胞色素Ｐ４５０酶主要参与外来化合物进入体内后的第一阶段激活反应。Ｐ４５０酶具有催化特异性，同种Ｐ４５０酶在人群中可以表现为不同表型，这种遗传多态现象决定Ｐ４５０酶对特定的外来化合物在反应上的各异，即表现为个体对环境致癌剂的不同易感性。     

健康汉族人细胞色素P450 2Cl9基因的检测

目的了解广东地区汉族人细胞色素(P450 2C19)基因的分布情况. 方法应用PCR技术对正常人细胞色素(P450 2C19)基因进行扩增以SmaI进行限制性酶切图谱分析. 结果广东地区汉族人P450 2C19基因中,野生型纯合子(wt/wt) 频率是0.4454;CYP2Cl9杂合子(mt/ml) 频率是0.4091;CYP2Cl9 突变型纯合子(ml/ml)频率是0.1455.P450 2C19基因ml频率是0.3500,基因wt频率是0.6500. 结论广东地区汉族人的细胞色素CYP2C19基因频率与其它地区人群相接近.     

细胞色素P450基因多态性与药物代谢

细胞色素P450(cytochrome P450,CYP)在众多外源性和内源性物质的代谢中具有重要作用.CYP家族1-3中编码P450的基因均存在多态性,特别是CYP2C9、CYP2C19、CYP2D6和CYP3A5.超过一半的临床药物是由多态性P450介导代谢,CYP基因的多态性是造成药物反应个体差异的主要原因.近几年,许多与P450酶活性和CYP基因表达相关的等位基因已被鉴定,因此通过分型CYP基因的功能性或标签(Tag)的遗传变异,就可以获得个体的代谢表型,有助于医生及时找到正确的用药方案,有效地提高药物疗效和降低毒副作用,特别是那些治疗指数窄的药物.显然,了解CYP基因的遗传变异对于临床药物治疗和药物开发是必不可少的.基因芯片技术具有高多重水平和高通量的特点,使同时分型大量CYP基因遗传变异成为可能,是实现个性化医疗的重要技术保障.然而,DNA制备制约了预测性CYP基因分型芯片的发展,其在临床上的广泛应用尚需时日.     

细胞色素P450基因遗传多态性的研究进展

细胞色素P450（cytochrome P450，CYP）在众多外源性物质和内源性物质的代谢中具有重要作用。家族1-3中编码P450的基因均存在多态性，特别是CYP2C9、CYP2C19、CYP2D6和CYP3A5。超过一半的临床药物是由多态性P450介导代谢，CYP基因的多态性是造成药物反应个体差异的主要原因。近几年，许多与P450酶活性和CYP基因表达相关的等位基因已被鉴定，因此通过分型CYP基因的功能性遗传变异或标签（Tag）遗传变异，就可以获得个体的代谢表型，有助于医生及时找到正确的用药方案，有效地提高药物疗效和降低毒副作用，特别是那些治疗指数窄的药物。显然，了解CYP基因的遗传变异对于临床药物治疗和药物开发是必不可少。基因芯片技术具有高多重水平和高通量的特点，使同时分型大量CYP基因遗传变异成为可能，是实现个性化医疗的重要技术保障。然而，DNA制备制约了预测性CYP基因分型芯片的发展，其在临床上的广泛应用尚需时日。     

肝富集的转录因子与细胞色素P450基因的表达调控

细胞色素P450(cytochromeP450,CYP)是含血红素酶家族,广泛存在于从细菌到哺乳动物中,参与氧化或还原代谢多种内源和外源化合物。如内源性甾体激素、维生素和脂肪酸衍生物的合成与分解,外源性药物、杀虫剂、环境污染物和致癌物的代谢[1]。CYP1-4家族主要代谢外源化合物,它们表现     

中国汉族人细胞色素P450 2D6Ch基因特点研究

细胞色素Ｐ４５０２Ｄ６（ＣＹＰ２Ｄ６）基因的多态性是一种药物代谢的遗传变异，其表型分为强代谢型和弱代谢型。而且表型和基因的多态性存在明显的种族差异。本文利用ＰＣＲ－ＲＦＬＰ技术对１００名正常中国人ＣＹＰ２Ｄ６基因的Ｃｈ型突变特点做了分析，结果发现，在ＣＹＰ２Ｄ６基因的第１８８位点Ｃ→Ｔ的频率为０．５７，第４２６８位点Ｇ→Ｃ的频率为０．６６，而且Ｔ１８８／Ｔ１８８、Ｔ２９８８／Ｔ２９８８及Ｃ４２６８／Ｃ４２６８纯合子的比率分别为０．３２、０．０８和０．４２。与国外报道比较，发现中国人ＣＹＰ２Ｄ６基因的这两个位点的多态性分布规律与西方人有明显的不同。     

乙醇对肝细胞色素P-450氧化酶2E1的诱导

目的: 研究摄入乙醇对肝脏CYP450 2E1的诱导。方法: 18例不同程度酒精性脂肪性肝炎患者, 其中12例酗酒持续至肝活检术前1-3日内, 6例则已戒酒3周至7个月; 4例病因不明脂肪性肝炎患者, 但无酗酒史。采用免疫组化方法对肝组织切片进行CYP450 2E1染色及程度评估。结果: 近日仍酗酒的患者中肝组织切片CYP450 2E1的免疫组化染色显著强于已戒酒、无酗酒者。结论: 持续摄入乙醇能显著诱导CYP450 2E1, 但戒酒后乙醇的诱导作用可以随之减弱、消失。     

细胞色素P450 1A1在自然流产患者胎盘绒毛组织中的表达及意义

目的　探讨细胞色素P4 5 0 1A1(CYP1A1)mRNA在自然流产患者胎盘绒毛组织中的表达及其意义。方法　采用半定量逆转录聚合酶链反应 (RT -PCR)法检测 4 5例自然流产患者 (研究组 )中及 30例正常妊娠孕妇 (对照组 )胎盘绒毛组织中CYP1A1mRNA的表达。结果　自然流产及正常妊娠胎盘绒毛组织中CYP1A1mRNA相对表达强度分别为 0 .5 6± 0 .2 0、0 .35± 0 .14、两组比较差异显著 (P <0 .0 1)。自然流产患者中孕期有被动吸烟及孕期有饮茶或咖啡习惯者的胎盘绒毛组织中CYP1A1mRNA表达最强。结论　胎盘绒毛组织中CYP1A1mRNA表达增强可能与自然流产的发生相关 ,同时可在一定程度上说明孕妇吸烟、被动吸烟及摄入过多咖啡因可通过增强胎盘绒毛组织中CYP1A1的转录水平而增加自然流产的风险。     

细胞色素P450 2A6的多态性研究

细胞色素P450 2A6(cytochrome P450 2A6，CYP2A6)是主要的尼古丁C-氧化酶和香豆素7-羟化酶。对已发现的CYP2A6的等位基因及其对CYP2A6活性的影响，CYP2A6的多态性和个体吸烟行为及肺癌、食管癌的易感性的关联进行综述。     

Activity of cytochrome P450 in children

The 6β-hydroxycortisol/cortisol ratio was measured in 52 children aging 1.1–14.0 years. The maximum increment in this ratio occurred in the age interval of 1.1–2.0 years. During this period, the regression coefficients in the linear (r=0.57;p=0.044) and nonlinear logarithmic models (r=0.56;p=0.049) were similar. At the age of 10–14 years, the examined ratio attained 19.17±17.79. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 9, pp. 272–274, September, 2004     

Activity of cytochrome P450 in children

The 6-hydroxycortisol/cortisol ratio was measured in 52 children aging 1.1–14.0 years. The maximum increment in this ratio occurred in the age interval of 1.1–2.0 years. During this period, the regression coefficients in the linear (r=0.57; p=0.044) and nonlinear logarithmic models (r=0.56; p=0.049) were similar. At the age of 10–14 years, the examined ratio attained 19.17±17.79.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 9, pp. 272–274, September, 2004     

Examination of cytochrome P450 content of primary porcine hepatocyte cultures with various media formulations for use in bioartificial liver devices

Primary porcine hepatocytes (PPHs) are used in most bioartificial liver devices (BALs). Liver-specific function, however, deteriorates in these cells in culture. In this study, the PPH biotransformation profile was analyzed over a 6-day culture period, in four separate serum-free media formulations using total cytochrome P450 (P450) content as a marker of differentiation. The general health of the cells in culture was evaluated by analysis of cell morphology, total protein (TP) content, and viability. The total P450 content of bovine adrenocortical cells (BACs) was also evaluated for comparison with hepatocytes. Freshly isolated hepatocyte P450 levels were 120 ± 34 pmol/mg TP, which decreased rapidly in the first 2 days in culture in all media before maintaining P450 levels at between 17 and 28 pmol/mg TP (14%–23% of fresh cell values) at day 6 in culture. Williams' E Medium showed a significantly lower P450 level (25 ± 3 pmol/mg TP) than Hepatocyte Medium (35 ± 3 pmol/mg TP; P = 0.043) on day 4. Williams' E Medium also showed a significantly lower P450 level (17 ± 1 pmol/mg TP) on day 6 than Medium 199 (25 ± 1 pmol/mg TP; P = 0.026) and RPMI-1640 (27 ± 5 pmol/mg TP; P = 0.033). BAC P450 levels decreased to a similar but greater extent to PPHs, decreasing from a fresh cell level of 429 pmol/mg TP to 58 pmol/mg TP (13% fresh cell value) after 6 days in culture. PPHs and BACs show a similar pattern of total P450 decrease in culture. However, Williams' E Medium maintains lower P450 biotransformation potential compared to the other test media studied and is therefore not recommended for use in a BAL. Received: February 19, 2001 / Accepted: July 30, 2001     

Expression of selected cytochrome P450 isoforms and of cooperating enzymes in colorectal tissues in selected pathological conditions

The current interest in CYP expression in the colon results from its uniqueness as a target organ for cancer.     

Changes in cytochrome P450 side chain cleavage expression in the rat hippocampus after kainate injury

Our previous study showed an increase in total cholesterol level of the hippocampus after kainate-induced injury, but whether this is further metabolized to neurosteroids is not known. The first step in neurosteroid biosynthesis is the conversion of cholesterol to pregnenolone by the enzyme cytochrome P450 side chain cleavage (P450scc). This study was carried out to elucidate the expression of this enzyme in the kainate-lesioned rat hippocampus. A net decrease in P450scc protein was detected in hippocampal homogenates by Western blots at 2 weeks post-kainate injection (time of peak cholesterol concentration after kainate injury). Immunohistochemistry showed decreased labeling of the enzyme in neurons, but increased expression in a small number of astrocytes. The level of pregnenolone was also analyzed using a newly developed gas chromatography–mass spectrometry (GC–MS) method, optimized for the rat hippocampus. A non-significant tendency to a decrease in pregnenolone level was detected 2 weeks post-lesion. This is in contrast to a large increase in oxysterols in the lesioned hippocampus at this time (He et al. 2006). Together, they indicate that increased cholesterol in the kainate lesioned hippocampus is mostly metabolized to oxysterols, and not neurosteroids. Wan-Jie Chia and Andrew M. Jenner contributed equally to this work.