Peroxisome proliferation and hepatocarcinogenesis.
Peroxisome proliferation and hepatocarcinogenesis.
复制标题
过氧化物酶体增殖和肝癌发生。
DOI：
10.1093/carcin/8.5.631
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发表时间：
1987
期刊：
影响因子：
4.7
通讯作者：
Reddy,JK
中科院分区：
文献类型：
--
作者：
Rao,MS;Reddy,JK
过氧化物酶体增殖剂是一类新型的非致突变性肝癌致癌物，它们都能诱导类似的多效性反应，包括肝肿大、肝实质细胞中过氧化物酶体的增殖和几种肝酶的诱导，尤其是过氧化物酶体脂肪酸/3-氧化系统的酶（1-3）。目前，几种结构不同的降血脂化合物，包括广泛使用的药物氯贝特和某些邻苯二甲酸酯增塑剂，是公认的过氧化物酶体增殖剂的两大类(2)。由于这些药物缺乏致突变性，因此有人提出，肝癌的发生与这些化学物质（或其可能的代谢物）的直接启动作用无关，而是与肝细胞中过氧化物酶体数量持续增加所引起的代谢紊乱有关(4)。因此，阐明这些药物诱导过氧化物酶体增殖和相关酶的机制被认为是必要的，以便了解这些似乎不与DNA相互作用和损害DNA的外源性药物诱导的肝癌发生中的过氧化物酶体的作用（5,6）。本文简要回顾了过氧化物酶体增殖物的生物学效应，以及诱导多效性反应的可能机制，从而导致肝细胞癌的发生，重点讨论了这些物质通过与特定受体相互作用来发挥作用的假设。
Peroxisome proliferators constitute a novel class of non-mutagenic hepatocarcinogens, all of which induce a similar pleiotropic response consisting of hepatomegaly, proliferation of peroxisomes in the liver parenchyma] cells and the induction of several hepatic enzymes, particularly those of the peroxisomal fatty acid/3-oxidation system (1—3). Presently several structurally dissimilar hypolipidemic compounds, including the widely used drug clofibrate, and certain phthalate ester plasticizers are the two major categories of agents that are recognized as peroxisome proliferators (2). The lack of mutagenicity of these agents led to the proposal that hepatocarcinogenesis is not related to the direct initiating effect of these chemicals (or their possible metabolites), but linked to metabolic disturbance (s) emanating from sustained increase in the number of peroxisomes in liver cells (4). Elucidation of the mechanism of induction of peroxisome proliferation and associated enzymes by these agents is, therefore, considered essential in order to understand the role of peroxisomes in liver carcinogenesis induced by these xenobiotics which do not appear to interact with and damage DNA (5, 6). This commentary is a brief review of the biological effects of peroxisome proliferators and of possible mechanisms of induction of pleiotropic responses leading to the development of hepatocellular carcinomas, focusing in particular on the hypothesis that these agents exert their effects by interacting with a specific receptor (s).