The importance of nuclear damage depends on the fact that the cell nucleus contains the genetic information upon which all the vital activities of the cell ultimately depend. Severe nuclear damage indicated by pyknosis and karyolysis are customarily taken as evidence of cell necrosis.It should be remembered, however, that the red cells, although devoid of a nucleus maintain selective membrane permeability, prodouce energy by anaerobic glycolysis and perform their vital speacialised function of oxygen transport in the blood for over 100 days in man. Protozoa such as Amoeba proteus survive at least several days following microsurgical removal of their nucleus:motility and phagocytic activity are arrested but these return, together with the ability to reproduce, when the nucleus from another amoeba is introduced. It is therefore clear that cells can survive despite total cessation of nuclear function; their metabolic versatility will, however, be greatly reduced and their ability to multiply lost.
细胞核损伤
细胞核损伤的重要意义在于核含有细胞一切生命活动所必需的遗传信息。表现为核浓缩和核溶解的严重核损伤通常被认为是细胞坏死的证据。然而应该记住，红细胞虽然没有细胞核，但保持选择性膜渗透性，并通过无氧糖酵解产生能量，在人类红细胞可执行其与生命攸关的运输氧的特殊功能一百多天。原虫如阿米巴用显微外科手术摘除其核之后至少可存活数天。这时运动和吞噬能力减弱，但其从另一个阿米巴取出的核植入时，这些功能和生殖能力都可恢复。因此，很清楚，尽管核功能完全停止，细胞然能存活，可是其各种代谢功能大大降低，生殖能力丧失。
Gene mutation
Perhaps the best understoood form of nuclear damage is that due to irradiation or to mutagenic chemicals such as nitrogen mustards. These and other unidentified factors may result in errors in DNA molecules. If the damage is sufficiently localised, e.g. affecting only one base, it is most unlikely to lead to an alteration in the nucleus demonstrable by avaible chemical or morphological techniques. Its presence may be inferred if there is a familial disease which can be shown to be due to genetic rather than purely environmental factors. Such disease are essentially mediated by an abnormal gene resulting in incorporation of a ‘wrong’ amino acid at a functionally important part of a protein molecule, or by deletion of a gene with consequent absence of the protein. In most known examples, the affected proteins are enzymes, as in phenylketonuric oligophrenia which affects 1 in 10,000 of the population. It is due to deficiency in the liver cells of phenylalanine hydroxylase, which normally converts phenylalanine to tyrosine, and brain damage apparently results from raised blood and cerebrospinal fluid levels of phenylalanine and its metabolites. There are also many genetic abnormalities of haemoglobin (haemoglobinophathies), the sickle cell abnormality being a good example. Other carrier proteins, for example transferrin which binds iron, many also be defective. Genetic abnormalities of cell surface receptors, e.g. for low density lipoprotein, have been described and there probably errors in genes coding for the polypeptide chains of structural proteins such as collagen and also for proteins which regulate the activity of other genes. Many of the so-called inborn errors of metabolism are inherited as a recessive trait─ i.e. are apparent only in the homozygous individual, although sometimes the symptomless heterozygote can be identified by demonstrating subnormal activity of the gene product. It should be noted that similar but not identical genetic diseases may result from mutations affecting different genes concerned in a particular function, for example the various factors involved in blood coagulation, or from different mutations affecting a single gene and causing various degrees of functional impairment of the gene product. The influence of environmental factors in causing lesions may result in variations among individuals with an identical genetic abnormality, for example the severity of brain damage in phenylketonuric oligophrenia(see above) is influenced by the amount of phenylalanine in the diet.
基因突变
人们了解得最清楚的一种核损伤类型，可能是由于放射或诱变的化学物质（如氮芥类）所导致的核损伤。这些和其他未查明的因素可导致DNA分子的嘌呤和嘧啶碱基排列顺序错误。如果损伤很局限，例如仅累及一个碱基，则所引起的核变化，用现在的化学或形态学技术显示的可能性极小。如果能证明是由于遗传因素而不是单纯环境因素所引起的家族病，则可推论出发生了核变化。这种疾病实质上是由一个异常基因或一个基因缺陷所导致。前者导致一个“错误”的氨基酸结合在一个蛋白质分子具有重要功能的部位，后者则可造成蛋白质的缺乏。在已知的大部分病例中受损的蛋白质是酶，如苯丙酮尿酸精神幼稚病，患者占人口的万分之一，是由于在正常情况下使苯基氨基酸转变为酪氨酸的肝细胞苯基丙氨酸羟化酶缺乏所致，因此血液和脑脊液的苯基丙氨酸和其代谢产物水平升高而引起脑损伤。血红蛋白也有许多遗传异常（血红蛋白病），其中镰状细胞异常就是一个很好的例子。其他的现代2蛋白，例如结合铁的转铁蛋白也可发生缺陷。细胞表面受体遗传异常，例如低密度脂蛋白的受体已被描述，在为结构蛋白（如胶原）多肽链编码的基因中也可能有错误。许多所谓的后天性代谢错误有隐性遗传特性，即仅在纯合子个体才显现，但是有时无症状的杂合体也能通过证明其基因产物活性低于正常来识别。应当注意，相似但不完全相同的遗传病可由于累及与某一功能有关的不同基因，例如在血凝系统中不同因子，突变所造成的或由于累及单一基因日发生不同的突变并使该基因产物产生不同程度的功能损害。环境因素的影响可以在具有同一种遗传个体中引起不同的损害。例如苯丙酮尿酸精神幼稚病（见上述）脑损害的严重程度受事物中苯基丙氨酸含量的影响。
Some genetic disorders are evident at birth (i.e. are congenital), particularly those resulting in abnormalities of physical development. For example, an excess of the androgenic steroid 17 α-hydroxyprogesterone may have masculinising effect on the development of the external genitalia of a female child. This is due to genetic deficiency of the adrenocortical enzyme which normally converts that substrate to a nonandrogenic steroid in the biosynthesis of cortisol. Other genetic disorders become apparent when the demands of an independent existence after birth reveal a disorder of function such as renal failure, increased susceptibility to infection, or mental deficiency. Some genetic disorders are first recognized later in childhood or ever in adult life because of the existence of metabolic pathways or functions peculiar to later periods of life or to the cumulative effects of factors which injure the genetically abnormal cells. The number of genetic disorders of metabolism is increasing rapidly, although the biochemical basis of many has not yet been elucidated. In recent years it has become possible to diagnose certain genetic abnormalities by investigation of fatal cells obtained in aspirated amniotic fluid and this has sometimes provided the opportunity to terminate pregnancy before the fetus is viable.
一些遗传病在出生时已很明显（即先天性的），特别是那些导致身体发育畸形的遗传病。例如，过多的产生男性特征的类固醇（17-羟孕酮）可影响女孩的外生殖器的发育，使之男性化。这是由于在皮质醇生物合成中将底质转变为非产生男性特征类固醇的肾上腺皮质酶遗传缺陷所致。当出生后小儿独立生存的需求呈现功能紊乱（如肾功能衰竭对感染敏感性增高或智力缺陷）时，另一些遗传病就变为明显。有些遗传病，在童年期后期甚至在成年期，才被发现，这是因为有代谢旁路存在或在人生后期所特有的功能，或者是因为某些因素对遗传异常细胞损伤作用需要多年的累积。代谢性遗传病的数目迅速增加，但是许多这类病的生化基础尚未得到阐明。近年来已能通过检查吸取羊水中的胎儿细胞诊断一些遗传异常，并因此有时在胎儿成熟前终止妊娠。
In the above examples the mutation has occurred in a germ cell and is transmitted to the descendents of the affected individual, resulting in a familial pattern of disease. Mutation can also occur in cells other than germ cells-somatic mutation – but this is likely to be apparent only when the genetically altered cell proliferates abnormally to form a large family or clone of similar cells, e.g. when a tumour forms.
上述例子中生殖细胞已发生突变，且传递给患者后代，导致一家族疾病的模式。突变也可发生于生殖细胞以外的细胞（体细胞突变），但这很可能仅表现于遗传性改变的细胞异常增生而形成一大系或克隆的相似的细胞时，例如当一个肿瘤形成时。
An interesting abnormality encountered in many types of tumour is the synthesis of substance normally restricted to fetal life, e.g. α-fetoprotein (normally produced by fetal hepatocytes) by liver cell cancer in the adult. Some tumours produce compounds characteristic or other tissues, e.g. parathyroid hormone by cells of tumour arising in the bronchus. The mechanism of the underlying disorder of genetic control in such tumours is unknown.
在许多类型肿瘤中出现一种使人关注的异常，是合成在正常情况下限于胎儿期形成的物质，例如成人肝细胞癌产生甲胎蛋白（在正常情况下，由胎儿肝细胞产生）。一些肿瘤产生具有其他组织特征的复合物，例如来源于支气管的瘤细胞产生甲状旁腺激素。这种肿瘤遗传控制的潜在性紊乱机制尚不清楚。
