Mouse skin models for carcinogenic hazard identification: utilities and challenges.
Mouse skin models for carcinogenic hazard identification: utilities and challenges.
复制标题
用于致癌危害识别的小鼠皮肤模型：实用性和挑战。
DOI：
10.1080/01926230701748131
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发表时间：
2007
影响因子：
1.5
通讯作者：
Hansen,LauraA
中科院分区：
文献类型：
--
作者：
Lynch,Dave;Svoboda,Jessica;Putta,Sumanth;Hofland,HansEJ;Chern,WendyH;Hansen,LauraA
本报告讨论了1）用于致癌危害识别的小鼠皮肤模型的可预测性，2）皮肤早期变化与后期致瘤反应之间的相关性，以及3）三种皮肤肿瘤发生小鼠模型的相对敏感性;即遗传启动的Tg.AC和RasH 2系以及SENCAR小鼠模型。所有三种小鼠模型对局部药物治疗数周的反应相似，均为轻度炎症和表皮增生。根据我们以前的研究经验，我们假设皮肤中的炎症、刺激、增殖和/或增生将先于并预测这些敏感小鼠皮肤模型中肿瘤的出现。与我们的假设一致，试验药物在Tg.AC小鼠中引起了低但显著的致瘤反应。我们认为炎症、刺激和增生是Tg.AC小鼠后期致瘤反应的敏感预测因子。然而，需要进一步的研究来更好地确定这3种模型对更广泛的药物的相对敏感性。
This report addresses 1) the predictability of mouse skin models for carcinogenic hazard identification, 2) the association between early changes in the skin and later tumorigenic responses, and 3) the relative sensitivity of three mouse models of skin tumorigenesis; i.e. the genetically-initiated Tg.AC and RasH2 lines and the SENCAR mouse model. All three mouse models responded similarly, with mild inflammation and epidermal hyperplasia, to several weeks of treatment with a topical agent. Based on our previous research experience, we hypothesized that inflammation, irritation, proliferation, and/or hyperplasia in the skin would precede and predict the appearance of tumors in these sensitive mouse skin models. Consistent with our hypothesis, the test agent caused a low but significant tumorigenic response in Tg.AC mice. We propose that inflammation, irritation, and hyperplasia are sensitive predictors of a later tumorigenic response in Tg.AC mice. Further studies are needed, however, to better determine the relative sensitivity of these 3 models to a wider variety of agents.