Long Gerald G, Morton Daniel, Peters Terry, Short Brian, Skydsgaard Mikala
Lilly Research Laboratories, Indianapolis, Indiana 46225, USA.
Toxicol Pathol. 2010 Jan;38(1):43-50. doi: 10.1177/0192623309354107. Epub 2009 Nov 13.
The Carcinogenicity Alternative Mouse Models (CAMM) Working Group of the Society of Toxicologic Pathology (STP) surveyed the membership to define current practices and opinions in industry regarding the use of alternative mouse models for carcinogenicity testing. The results of the survey indicated that CAMM are used most often to fulfill a regulatory requirement (e.g., to replace the two-year mouse bioassay) and are being accepted by regulatory agencies. Alternative models are also sometimes used for internal decision making or to address a mechanistic question. The CAMM most commonly used are the p53+/- and rasH2. The rasH2 appears to be the currently accepted model for general carcinogenicity testing. Problems with study interpretation included lack of historic background data, unexpected tumor finding, and tumor identification/characterization of early lesions. Problems with implementation or conduct of the study included extent of the pathology evaluation, numbers of animals, survival, and study duration. Recommendations were developed for, frequency and type of positive control testing, extent of histopathologic examination of test article-treated and positive control animals, current use and future development of diagnostic criteria; increased availability and use of historic data, and use of other genetically modified mice in carcinogenicity testing.
毒理病理学会（STP）的致癌性替代小鼠模型（CAMM）工作组对其成员进行了调查，以确定行业内目前在使用替代小鼠模型进行致癌性测试方面的做法和观点。调查结果表明，CAMM最常用于满足监管要求（例如，替代两年期小鼠生物测定），并且正在被监管机构所接受。替代模型有时也用于内部决策或解决机制问题。最常用的CAMM是p53+/-和rasH2。rasH2似乎是目前普遍致癌性测试所接受的模型。研究解读方面的问题包括缺乏历史背景数据、意外的肿瘤发现以及早期病变的肿瘤识别/特征描述。研究实施或开展方面的问题包括病理评估的范围、动物数量、存活率和研究持续时间。针对阳性对照测试的频率和类型、受试物处理动物和阳性对照动物的组织病理学检查范围、诊断标准的当前应用和未来发展；增加历史数据的可获取性和使用，以及在致癌性测试中使用其他基因改造小鼠等方面提出了建议。
