摘要
目的:恶性肿瘤是目前临床上的常见疾病,是威胁人类健康和导致死亡的主要原因之一。因而征服肿瘤成为当今生物医学界的一个重大科研课题。虽然人们已经做了大量的工作,但至今尚未取得决定性突破,究其根本的原因是肿瘤发生机制不清楚。所以研究肿瘤的本质,探讨肿瘤的发生机制具有重要意义。
活性氧(reactive oxygen species,ROS)指较O_2的化学性质更为活跃的O_2代谢产物及其衍生的含氧物质的统称,包括所有的含氧自由基和过氧化物。适量的ROS参与增殖、分化、凋亡相关的信号转导途径,发挥着重要的生理功能。但过量的ROS对机体多种结构造成可逆/不可逆的损伤,引发多种临床疾病。ROS与肿瘤的发生发展密切相关。但其中的机制仍不清楚。线粒体是细胞的动力工厂,在细胞多种生理病理过程中发挥着重要作用;同时氧化呼吸链的电子漏又是机体ROS的最主要来源,研究线粒体ROS在肿瘤发生发展中的作用具有重要意义。
方法:本文以线粒体为研究核心,以ROS的产生和清除为主线,采用成纤维细胞转化和恶性转化模型,深入探讨线粒体微环境ROS平衡在肿瘤的发生发展中的地位和作用。具体工作包括:(1)MNNG诱导小鼠成纤维细胞转化作用;(2)TPA促进MNNG诱导的成纤维细胞恶性转化作用;(3)H_2O_2促进MNNG转化成纤维细胞恶性转化作用;(4)抗氧化剂等对已经恶性转化、获得永生化的成纤
AIM:Tumor is a kind of disease which can rob many pepole of their happy lives or even lead to death. But up to now, we still haven't effective ways to prevent or cure it because the nature of tumor is unclear. So it is important to study the happenning mechanisam of tumor.Reactive oxygen species (ROS) including oxygen free radical and hyperoxide, are more active than O_2, which play an important role in cell proliferation, differentiation,apoptosis and some other metabolize activities.But excessive ROS can induce the injury to the cell which lead to many clinical diseases.ROS are closely related to the tumor.The mitochondria is a important organelle which provide the energy to the cell and participate in many cell metabolize activities.At the same time,mitochondrial electron transport chain is the major source of ROS. The mitochondrial ROS maybe a factor in carcinogenesis.We hypothesis that the imbalance of redox in mitochondria is the main cause of carcinogenesis .The rising ROS in mitochondria induce the cell to proliferate unconventionally and finally the happenning of tumor.METHODS:In this study,we establish three fibroblast transformation models and investigate the change ROS in mitochondria and other related datas to analyze the action of ROS in mitochondria in carcinogenesis.The experiments include: (1)Fibroblast transformation induced by MNNG.(2) Fibroblast malignant
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