A matter of life and deathNO.2
2A matter of life and death
CONCEPTION and cancer, which mark the beginning and, often, the end of life, share some molecular details. Cancer cells copy their contents and divide rapidly; so do newly fertilized eggs. This requires genetic reprogramming. Curiously, as a result of the reprogramming, both contain appreciable amounts of an enzyme called reverse transcriptase that biologists more usually associate with certain viral infections, including HIV. Reverse transcriptase makes part of the cell’s protein publishing line work backwards, recreating DNA, a molecule in which organisms typically store genetic information, from its less stable and correspondingly less favoured cousin, RNA. Why it does so in cancer and in embryos, though, is something of a mystery.
Corrado Spadafora, of Italy’s National Institute of Health, in Rome, studies this littleknown puzzle. There are thousands of reversetranscriptase genes in the genomes of all mammals. What that job is exactly, Dr Spadafora is not sure, but data he presented at the annual meeting of the British Andrology Society, in Leeds, suggest some answers.
Dr Spadafora showed recently that reverse transcriptase is required for mouse embryos to develop. He did this by removing it in two ways. First, he exposed embryos created in Petri dishes to a common AIDS drug called nevirapine, which works by gumming the enzyme up. This halted development whenever it was added to embryos up to the stage when they were only four cells big. Adding the drug later, when the four cells had divided into eight, had no effect. Second, he checked the drug was not bad for the embryos in some other, unknown, way by specifically turning off reverse transcriptaseproducing genes. The result was the same: the embryos did not die, and again, during the sensitive period, they seemed to get stuck in a juvenile stage.
There are hints that reverse transcriptase is needed for a lot of early embryonic functions associated with getting cells ready to specialize into different types of tissue. Seven of the ten genes Dr Spadafora tested were active in healthy embryos, but were shut down in the nevirapine arrested ones.
Since cancer cells also contain a lot of reverse transcriptase, Dr Spadafora wondered whether stopping the enzyme working might stop them dividing as well. He transplanted four kinds of human cancer into four groups of mice and treated some of each group with nevirapine or a similar drug. In all cases the earlier he gave the drug, the slower the tumours grew, and they always grew more slowly than tumours in mice which got neither drug. As in the embryo experiments, he then silenced the cancercell genes that produced reverse transcriptase, and likewise found the tumours grew more slowly.
Moreover, both the drugs and the genesilencing technique flattened some types of cancer cells, which suggests that both methods of getting rid of reverse transcriptase’s effects caused similar molecular changes inside the cells.
That common antiHIV drugs slow cancer growth in AIDS patients has been known for some time. Doctors, however, have attributed the fact to the healthier immune systems the drugs promote. Dr Spadafora’s results suggest a more precise mechanism.
molecular［mEu5lekjulE］
a.分子的，由分子组成的
［真题例句］ But NBAC members are planning to word the recommendation narrowly to avoid new restrictions on research that involves the cloning of human DNA or cellsroutine in molecular biology.［1999年阅读4］
［例句精译］ 但是，NBAC成员们正计划在建议的措辞上更为严谨，以避免给克隆人体DNA或细胞等研究带来更多地限制——（这属于）分子生物研究中的常规课题。
reverse［ri5vE:s］
n.①相反，反转，颠倒；②背面，后面；a.相反的，倒转的；v.颠倒，倒转，（使）倒退
［真题例句］ Anyone can see this trend is unsustainable.Yet few seem willing to try to reverse (v.) it.［2003年阅读4］
［例句精译］ 任何人都明白这个趋势不能维持下去，但是很少有人愿意扭转它。
expose［iks5pEuz］
v.①（to）使暴露，受到；②使曝光；③揭露
［真题例句］ (73) Owing to the remarkable development in masscommunications, people everywhere are feeling new wants and are being exposed (①) to new customs and ideas, while governments are often forced to introduce still further innovations for the reasons given above.［2000年翻译］
［例句精译］ （73）大众通讯的显著发展使各地的人们不断感到有新的需求，不断接触到新的习俗和思想，由于上述原因，政府常常得推出更多的革新。
juvenile［5dVu:vinail］
a.青少年的，幼稚的；n.青少年，少年读物
［真题例句］ Many theories concerning the causes of juvenile (a.) Delinquency (crimes committed by young people) focus either on the individual or on society as the major contributing influence.［2004年完形］
［例句精译］ 有关少年犯罪的许多理论往往将其主要原因归咎于个人或社会.
immune［i5mju:n］
a.①免疫的，有免疫力的；②不受影响的；③免除的，豁免的
［真题例句］ The rats (49：develop) bacterial infections of the blood , (50：as if) their immune (①) systems—the selfprotecting mechanism against disease—had crashed.［1995年完形］
［例句精译］ 老鼠患血液细菌感染，似乎它们的免疫系统——抵御疾病的自我保护机制——已崩溃。
precise［pri5sais］
a.精确的，准确的
［真题例句］ Much of the language used to describe monetary policy, such as “steering the economy to a soft landing” or “a touch on the brakes”, makes it sound like a precise science.［1997年阅读5］
［例句精译］ 很多用来描述货币政策的词，如“引导经济软着陆”，“经济刹车”，使货币政策听起来像是一门精确的科学。
反转录酶的发现
1970年Temin等在致癌RNA病毒中发现了一种特殊的DNA聚合酶，该酶以RNA为核板，根据碱基配对原则，按照RNA的核苷酸顺序(其中V与A配对)合成DNA。这一过程与一般遗传信息流转录的方向相反，故称为反转录，催化此过程的DNA聚合酶叫做反转录酶(reverse transcriptase)。后来发现反转录酶不仅普遍存在于RNA病毒中，哺乳动物的胚胎细胞和正在分裂的淋巴细胞中也有反转录酶。
反转录酶的发现对于遗传工程技术起了很大的推动作用，目前它已成为一种重要的工具酶。用组织细胞提取mRNA并以它为模板，在反转录酶的作用下，合成出互补的DNA (cDNA)，由此可构建出cDNA文库 (cDNA library)，从中筛选特异的目的基因，这是在基因工程技术中最常用的获得目的基因的方法。
生和死的问题
怀孕与癌症，前者是生命的开端，后者是生命的结束，但这两者在分子程度的细节上却有着相同之处。癌细胞复制自身并且快速分裂；新受精的卵细胞也一样。两者都要求基因的重组。令人好奇的是，作为重组的结果，这两者都包含一种为数不少的生物酶——反转录酶，生物学家通常将这种酶与某些病毒性感染联系在一起，包括HIV。反转录酶使部分细胞的蛋白质链反向工作，反向复制和DNA类似但较不稳定且相对而言并不重要的分子RNA，重新生成DNA——一种典型的储存了生物基本遗传信息的分子。为什么癌症和胚胎有这些相同点仍然是一个谜。
罗马意大利国家健康学院的Corrado Spadafora就在研究这个鲜为人知的难题。在所有哺乳动物的基因组中有上千个反转录酶的基因。Spadafora博士不敢肯定到底该做什么工作，但是他在利兹英国男科学会年会上提交的资料指出了某些答案。
Spadafora博士最近表示反转录酶在老鼠胚胎的发育中是必需的。他用两种方法除去反转录酶。第一种方法，他对在皮氏培养皿中生成的胚胎使用一种名为奈韦拉平的普通抗艾滋药物时，这种药物能破坏这种生物酶。在胚胎只有四个细胞的时候加入这种药物会停止细胞继续发育。如果晚一点、在胚胎分裂为8个细胞时加入药物则没有用。第二种方法，他使用药物以一种没有其他副作用的不明方法来专门抑制反转录酶基因的产生。效果是一样的：胚胎并没有死去，另外，在这个敏感的时期，他们似乎停留在了这个不成熟的阶段。
有线索显示，在早期假如胚胎想要实行将细胞转化为不同种类的组织的功能，反转录酶是必需的。在Spadafora博士测试的10个基因中，有7个基因在健康的胚胎中是活动的，但在加入了奈韦拉平的胚胎中则没有活动。
因为癌细胞同样含有许多反转录酶，Spadafora博士很想知道是否停止这种生物酶的作用同样会阻止细胞分裂。他将四种人类癌细胞移植到四组老鼠的体内，每一组用奈韦拉平或其他类似的药来治疗。在所有的试验中，越早给药肿瘤长得越慢，而且总是比没有用药的老鼠体内的肿瘤长得慢。而在胚胎试验中，他抑制了产生反转录酶的癌细胞的基因，同样发现肿瘤的生长变慢了。
而且，无论是药物还是通过基因沉默技术抑制致癌细胞，都说明去除反转录酶会导致细胞内部分子结构变化。
人们早就知道普通的抗艾滋病药物可以减缓艾滋病人的癌细胞生长。而医学界已经开始利用这一实际情况研究提高免疫系统的药物了。Spadafora博士的研究结果提供了更为具体的方法。
<PIXTEL_MMI_EBOOK_2005>21 </PIXTEL_MMI_EBOOK_2005> |
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