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首页> 外文期刊>The Internet Journal of Pharmacology >Protective action of EGCG against anticancer drugs MMS and CP
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Protective action of EGCG against anticancer drugs MMS and CP

机译：EGCG对抗癌药物MMS和CP的保护作用

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This experiment was conducted in order to assess the antigenotoxicity potential of Epigallocatechin-3-gallate (EGCG), a catechin, against genotoxicity induced by anticancer drugs, Methyl methanesulphonate (MMS) and cyclophosphamide (CP), in the form of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). These drugs were used at 60 ?M and 0.16 ?g/ml respectively along with EGCG at 10, 20, and 30 ?M in cultured human lymphocyte chromosomes. EGCG significantly reduced the genotoxic damage induced by the two drugs both in the presence and absence of metabolic activation system (S9 mix), although with greater effectiveness in the presence of metabolic activation. Introduction Epigallocatechin-3-gallate (EGCG), a compound closely related to Epicatechin gallate (ECG), is a catechin and polyphenolic antioxidant plant metabolite found in abundance in various types of tea, derived from the tea plant Camellia sinensis 1 . It helps protect the skin from ultraviolet radiation-induced genotoxic damage and tumor formation 2 . Methyl methanesulphonate is a monofunctional alkylating agent having neoplastic and mutagenic properties. It alkylates DNA at the N-7 position of guanine and N-3 position of adenine and these changes may result into abnormal base pairing at DNA replication 34 . Methyl methanesulphonate has been shown to induce sister chromatid exchanges in human lymphocytes 5678 . Cyclophosphamide is also an alkylating agent and after metabolic activation it gives rise to active mutagenic metabolic phospharamide mustard 9 . It reacts with electron-rich areas of vulnerable molecules like proteins and DNA 10 . EGCG was studied for its antimutagenic effect on the chromosomal aberrations and sister chromatid exchanges induced by methyl methanesulphonate and cyclophosphamide (known mutagens), both in the presence and absence of metabolic activation system in human lymphocytes in vitro. The aim of this study was to assess the antigenotoxic effect of EGCG, a catechin, against anticancer drugs such as MMS and CP, in order to reduce the genotoxic effect of such useful drugs. Methodology Chemicals Used: Cyclophosphamide (Sigma-Aldrich, New Delhi); Methyl methanesulphonate (Sigma-Aldrich); Sodium phenobarbitone (Sigma-Aldrich); Colchicine (Microlab, USA); Dimethyl sulphoxide (Merck, New Delhi); Epigallocatechin-3-gallate (CAS No.: 989-51-5, Sigma-Aldrich); RPMI 1640 (GIBCO, Invitrogen, USA); Phytohaemagglutinin-M (GIBCO, Invitrogen); Antibiotic-antimycotic mixture (GIBCO, Invitrogen); Fetal serum - calf (GIBCO, Invitrogen); 5-bromo-2-deoxyuridine (Sigma-Aldrich); Hoechst 33258 stain (Sigma-Aldrich); Giemsa stain (Merck); Mitomycin-C (Sigma-Aldrich); NADP (SRL, New Delhi). Human Lymphocyte Culture: Duplicate peripheral blood cultures were conducted according to Carballo et al. 11 . First, 0.5 ml of heparinized blood sample was obtained from a healthy donor (with permission of the Human Ethical Committee of the department) and was placed in a sterile tube containing 7 ml of RPMI (medium) 1640, supplemented with 1.5 ml of fetal calf serum and 0.1 ml of phytohaemagglutinin. These tubes were placed in an incubator at 37 ° C for 24 hours. Untreated culture and also negative and positive controls were run simultaneously. Chromosomal Aberration Analysis: Chromosomal aberration studies were conducted because an increase in the occurrence of aberrations in blood lymphocytes indicates the genotoxic potential of many drugs which are commonly used and also a greater risk of cancer. MMS at 60 μM concentration was dissolved in dimethylsulphoxide and was added later after 24 h. The cells were cultured for another 48 h at 37 ° C keeping them in an incubator. For metabolic activation experiments, 0.5 ml of S9 mix dose was added to the MMS treatment. S9 mix was prepared from the livers of healthy rats (with permission of the institutional Animal Ethical Committee to take liver from Wistar strain rats) as per standard procedure of Maron and Ames 12 .
机译：进行此实验是为了评估儿茶素表没食子儿茶素-3-没食子酸酯（EGCG）对抗癌药物甲磺酸甲酯（MMS）和环磷酰胺（CP）以染色体畸变（CAs）的形式产生的遗传毒性的潜在抗原毒性）和姐妹染色单体交换（SCE）。这些药物分别以60μM和0.16μg/ ml的浓度与EGCG以10μM，20μm和30μM的浓度用于培养的人淋巴细胞染色体中。 EGCG显着降低了两种药物在存在和不存在代谢激活系统（S9混合物）时引起的遗传毒性损害，尽管在存在代谢激活的情况下具有更大的有效性。简介Epigallocatechin-3-gallate（EGCG）是与Epicatechin gallate（ECG）密切相关的化合物，是一种从多种茶树中大量发现的儿茶素和多酚抗氧化剂植物代谢物，来源于茶树1。它有助于保护皮肤免受紫外线辐射引起的遗传毒性损害和肿瘤形成2。甲磺酸甲酯是一种具有肿瘤和诱变特性的单官能烷基化剂。它在鸟嘌呤的N-7位和腺嘌呤的N-3位使DNA烷基化，这些变化可能导致DNA复制34的碱基配对异常。甲磺酸甲酯已被证明可诱导人淋巴细胞5678中的姐妹染色单体交换。环磷酰胺也是一种烷基化剂，在代谢激活后，它会引起活性诱变的代谢磷酰胺酰胺芥菜9。它与脆弱的分子（如蛋白质和DNA 10）的富电子区域发生反应。研究了EGCG对在人淋巴细胞中是否存在代谢激活系统的情况下，由甲基磺酸甲酯和环磷酰胺（已知的诱变剂）诱导的染色体畸变和姊妹染色单体交换的抗诱变作用。这项研究的目的是评估儿茶素EGCG对抗癌药物（如MMS和CP）的抗原毒性作用，以降低此类有用药物的遗传毒性作用。使用的方法学化学方法：环磷酰胺（新德里西格玛奥德里奇）;甲磺酸甲酯（Sigma-Aldrich）;苯巴比妥钠（Sigma-Aldrich）;秋水仙碱（美国麦博实验室）;二甲基亚砜（默克，新德里）;表没食子儿茶素-3-没食子酸酯（CAS号：989-51-5，Sigma-Aldrich）; RPMI 1640（GIBCO，美国Invitrogen）;植物血凝素-M（GIBCO，Invitrogen）;抗生素-抗真菌混合物（GIBCO，Invitrogen）;胎儿血清-小牛（GIBCO，Invitrogen）; 5-溴-2-脱氧尿苷（Sigma-Aldrich）; Hoechst 33258染色剂（Sigma-Aldrich）; Giemsa污渍（Merck）;丝裂霉素C（Sigma-Aldrich）; NADP（SRL，新德里）。人淋巴细胞培养：根据Carballo等人的方法进行重复的外周血培养。 11。首先，从健康的供体（经部门人类伦理委员会许可）获得0.5 ml的肝素化血液样本，并将其放入装有7 ml RPMI（中）1640的无菌试管中，并补充1.5 ml胎牛犊。血清和0.1 ml植物血凝素。将这些管置于37℃的培养箱中24小时。未经处理的培养物以及阴性和阳性对照均同时进行。染色体畸变分析：之所以进行染色体畸变研究，是因为血液淋巴细胞中畸变发生率的增加表明许多常用药物具有潜在的遗传毒性，同时也增加了患癌的风险。将浓度为60μM的MMS溶解在二甲亚砜中，并在24小时后添加。将细胞在37°C下再培养48小时，将其置于培养箱中。对于代谢激活实验，将0.5 ml S9混合剂量添加到MMS处理中。按照Maron和Ames 12的标准程序，从健康大鼠的肝脏中制备S9混合物（经机构动物伦理委员会许可，从Wistar品系大鼠中提取肝脏）。

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