激素对癌变的调节作用。

W Lijinsky
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引用次数: 0

摘要

毫无疑问,激素在许多,也许是大多数癌症的发展中起着重要作用。这是因为它们对于维持多细胞生物体内的稳态至关重要。激素在这一过程中起重要作用的阶段尚不清楚,但动物实验表明,激素在开始、促进或进展中的干预可能很重要,假设这种整齐的划分与人类癌症的发展有关(Schmähl, 1985)。激素可以通过控制肝脏和其他器官中激活和解毒酶的水平来影响起始,从而影响动物所接触的致癌物的药代动力学。激素控制着某些器官的结构或功能成分的水平,例如,雄性大鼠肾脏中的α -2微球蛋白会影响对外来化学物质的处理。激素对动物的生长和发育有巨大的影响,并且肯定在众所周知的幼年动物(包括人类)对暴露于致癌物质的影响的高度易感性方面发挥了作用。在子宫内暴露于胎盘移植致癌物的动物,或在新生儿或婴儿时期暴露于单剂量致癌物的动物,经常会发生肿瘤,而这些肿瘤出现在成年后完全不接受治疗或暴露于更高剂量的动物身上。例如经胎盘暴露的啮齿动物的神经系统肿瘤(Ivankovic, 1979)和幼年啮齿动物的肝脏肿瘤(Vesselinovitch et al., 1979)。激素对细胞增殖的影响可能是这些影响的重要组成部分。从激素对动物致癌性影响的研究中,我们可以得出这样的结论:通过遗传、饮食、习惯、意外、疾病状态或性成熟而改变激素的功能可能会影响个体对致癌物的易感性,从而增加或减少患癌症的可能性。具有抗甲状腺特性的化合物(例如,硫脲嘧啶或乙烯硫脲,一种广泛用于农业和工业的许多硫氨基甲酸酯的污染物和副产品)或影响肾上腺或垂体分泌的物质可能与肿瘤发展的调节剂有关,这是根据上述动物实验得出的结论。阉割、衰老或性激素分泌过多也会调节致癌物质的影响,就像它们在实验动物身上所做的那样。其他激素如胰岛素、胃泌素、催乳素等的影响研究很少(Griffin et al., 1955),尽管这些重要激素在不同时间个体内的分布也有所不同。早期的一项研究(Sugiura和Benedict, 1933)未能显示出用多种激素治疗对几种移植肿瘤生长的影响。一个难以捉摸的谜团是,为什么雌激素和己烯雌酚在叙利亚仓鼠中引起肾脏肿瘤而不是乳腺肿瘤,而在大鼠中引起乳腺肿瘤而不是肾脏肿瘤。显然,为了更好地理解肿瘤转化和癌症发展的复杂性,我们需要了解更多的生物学知识。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Modulating effects of hormones on carcinogenesis.

There is no doubt that hormones have a role in the development of many, perhaps most, cancers. This is because they are vital in maintaining homeostasis in multicellular organisms in which cancer appears. The stage or stages at which hormones are important in the process are not known well, but experiments in animals indicate that hormonal intervention at initiation, promotion, or progression can be important, assuming that such neat division pertains to cancer development in humans (Schmähl, 1985). Hormones may affect initiation through control of the levels of activating and detoxifying enzymes in the liver and other organs, which affect the pharmacokinetics of carcinogens to which the animal is exposed. Hormones control the levels of structural or functional components of some organs, for example, the alpha-2 micro-globulin in the kidney of male rats, which affect the disposition of foreign chemicals. Hormones have enormous influence on growth and development of animals and must play a part in the well-known heightened susceptibility of young animals (including humans) to the effects of exposure to carcinogens. Animals exposed in utero to transplacental carcinogens, or those exposed to single doses as newborns or infants, frequently develop tumors that appear in animals treated as adults not at all or after exposure to much higher doses. Examples are nervous system tumors in rodents exposed transplacentally (Ivankovic, 1979) and liver tumors in rodents treated as infants (Vesselinovitch et al., 1979). It is probable that effects of hormones on cell proliferation are an important part of these effects. From the studies of hormonal effects on carcinogenesis in animals we can conclude that alterations in the function of hormones through inheritance, or through diet, habits, accidents, disease states, or sexual maturity could affect susceptibility of an individual to carcinogens, thereby increasing or decreasing the probability of developing cancer. Compounds with antithyroid properties (e.g., thiouracil or ethylene thiourea, a contaminant and by-product of many thiocarbamates widely used in agriculture and industry) or substances affecting adrenal or pituitary secretions might be implicated as modulators of tumor development, following the leads suggested by experiments in animals described above. Castration, aging, or hypersecretion of sex hormones would also modulate the effects of carcinogens, as they do in experimental animals. There have been few studies of the effects of other hormones such as insulin, gastrin, prolactin, and so forth (Griffin et al., 1955), although these vital hormones vary in distribution even within an individual at different times. An early study (Sugiura and Benedict, 1933) failed to show an effect of treatment with a variety of hormones on the growth of several transplanted tumors. One elusive mystery is why estrogens and diethylstilbestrol induce kidney tumors in Syrian hamsters but not mammary tumors, whereas in rats they give rise to mammary tumors but not to kidney tumors. Obviously we need to know much more about biology in order to better understand the intricacies of neoplastic transformation and development of cancer.

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