Interception of toxic agents/mutagens/carcinogens: some of nature's novel strategies.
Interception of toxic agents/mutagens/carcinogens: some of nature's novel strategies.
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拦截有毒物质/诱变剂/致癌物：大自然的一些新策略。
DOI：
10.1007/978-1-4684-5182-5_14
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Hartman,PE
中科院分区：
文献类型：
--
作者：
Hartman,PE
在本节重点讨论抗诱变剂和抗癌剂的作用机制时，值得注意的是防御机制的运作水平多种多样。大自然在每个层面上都提供了无数不同的例子。下面的描述主要围绕我自己的实验室多年来的利益流向进行。这些描述将重点介绍在这些有害分子攻击关键细胞（“干细胞”，参见参考文献 35）之前“拦截”潜在诱变剂和致癌物的众多机制中的一些机制，或者一旦进入关键细胞，在到达 DNA 之前，引发潜在的诱变损伤。这将是。人们默认 DNA 损伤是生命周期中局部损伤形成的最重要组成部分。正如其他地方所指出的，这种局灶性病变肯定不仅在致癌方面至关重要，而且在损害人类状况并共同构成生理“衰老”的一个重要方面的各种其他情况中也至关重要(27, 29)。当然有多种机制在生物体水平上发挥作用，以防止有毒物质的侵害；例如回避反应和反流。保护装置也在器官系统层面发挥作用。一个例子是哺乳动物的门静脉将同化分子输送到肝脏进行处理，然后再传播到生物体的其他部分。在本章中，我们着眼于组织水平上较低但同样重要的拦截水平，涉及酶的解毒，并且涉及重要但经常被忽视的细胞分子与潜在诱变剂/致癌物的直接相互作用。
In this section focused on mechanisms of action of antimutagens and anticarcinogens, it might be well to note that there are a wide variety of levels at which defense mechanisms operate. Nature provides numerous diverse examples at each level. The following descriptions center on the flow of interests of my own laboratory over a period of years. The descriptions will highlight a few of the many mechanisms that serve to" intercept" potential mutagens and carcinogens before these deleterious molecules can attack critical cells (" stem cells," see Ref. 35) or, once in a critical cell, before the DNA can be reached, to elicit a potentially mutagenic lesion. It will be. tacitly assumed that lesions in DNA are a most important component in formation of focal lesions during the lifespan. As pointed out elsewhere, such focal lesions are certain to be of critical importance not only in carcinogenesis but also in a wide array of additional situations that compromise the human condition and collectively constitute an important aspect of physiological" aging"(27, 29).There certainly are multiple mechanisms that operate at the organismal level to protect against toxic substances; examples are avoidance responses and regurgitation. Protective devices also operate at the level of organ systems. One example is the role in the mammal of the portal vein in delivering assimilated molecules to the liver for processing before dissemination to the rest of the organism. In this chapter we look at lower but equally important levels of interception that operate at the tissue level, that concern detoxification by enzymes, and that involve direct interaction of important but often neglected cellular molecules with potential mutagens/carcinogens.