用于人类风险评估的动物模型：过氧化物酶体增殖物激活受体α人源化小鼠。

Animal models for human risk assessment: the peroxisome proliferator-activated receptor alpha-humanized mouse.

作者信息

Gonzalez Frank J

机构信息

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Nutr Rev. 2007 Jun;65(6 Pt 2):S2-6. doi: 10.1111/j.1753-4887.2007.tb00323.x.

DOI:10.1111/j.1753-4887.2007.tb00323.x

PMID:17605307

Abstract

The hyperlipidemic fibrate drugs mediate their lipid-lowering effects through binding to and activating the peroxisome proliferator-activated receptor alpha (PPARalpha). PPARalpha ligands are potent hepatocarcinogens in rats and mice; after 11 months of feeding a fibrate drug, there is 100% incidence of adenomas and carcinomas. However, there is no evidence that humans chronically administered fibrates have increased cancer risk. Recent studies on PPARalpha-humanized mice have revealed a potential mechanism for the species differences in response to PPARalpha ligands. These models will be of great value in human risk assessment and in determining the mechanism of hepatocarcinogenesis.

摘要

高脂血症贝特类药物通过与过氧化物酶体增殖物激活受体α（PPARα）结合并激活该受体来介导其降脂作用。PPARα配体在大鼠和小鼠中是强效的肝癌致癌物；在给予贝特类药物喂养11个月后，腺瘤和癌的发生率为100%。然而，没有证据表明长期服用贝特类药物的人类患癌风险增加。最近对PPARα人源化小鼠的研究揭示了物种对PPARα配体反应差异的潜在机制。这些模型在人类风险评估和确定肝癌发生机制方面将具有重要价值。