Edler L, Schmidt R, Weber E, Rippmann F, Hecker E
Institute of Epidemiology and Biometry, German Cancer Research Center, Heidelberg.
J Cancer Res Clin Oncol. 1991;117(3):205-16. doi: 10.1007/BF01625426.
The initiation/promotion standard protocol 28 (protocol 28), developed and used previously as an experimental model to verify the cancerogenic process of initiation/promotion in mouse skin, was revised in three aspects: (a) statistically it was shown sufficient to use, per promoter dose group, 16 colony-outbred female NMRI mice: (b) by weekly individual records of tumor response (and health status) of each mouse in a dose group, cumulative tumor incidences (and mean and extreme body weights) are determined; from these data the collective records (tumor response, health status), the only data accessible from protocol 28, may be generated in addition; (c) the details of dose groups and all data on tumor response and health status are processed by computer using the program package PAPILLOM. The latter was developed specifically for this purpose, is written in the programming language APL and designed for easy handling by staff of animal laboratories. The program package calculates, from the individual records per promoter dose group, cumulative tumor incidences (and survival data) with confidence limits for any one exposure time, and the package may be linked to programs for statistical validations. In addition, from the collective records it calculates the tumor rates, tumor yields and survival rates for any one exposure time. These data, obtained by either of the standard protocols (16 or 28), are fully comparable. For pure compounds they may be used to calculate semiquantitative tumor-promoting potencies. These values for more than 80 polyfunctional diterpenes of the tigliane, ingenane and daphnane type, scattered in or calculated from previous papers, together with their irritancies, were compiled. Within recent years, computer-assisted standard protocol 16 has been used to handle and evaluate about 1000 promoter dose groups. Protocol 16 allows one to extract and utilize more and better toxicological information on tumor response and health status from any one dose group, utilizing significantly fewer experimental animals than required by protocol 28. Thus, the computer-assisted standard protocol 16 optimizes the utility of the experimental model of mouse skin for the amount, quality and management of experimental data as well as for the requirements of animal protection.
起始/促癌标准方案28（方案28），先前已被开发并用作实验模型来验证小鼠皮肤起始/促癌的致癌过程，该方案在三个方面进行了修订：（a）从统计学角度表明，每个促癌剂剂量组使用16只远交群雌性NMRI小鼠就足够了；（b）通过每周单独记录剂量组中每只小鼠的肿瘤反应（和健康状况），确定累积肿瘤发生率（以及平均体重和极端体重）；根据这些数据，还可以生成集体记录（肿瘤反应、健康状况），这是方案28中唯一可获取的数据；（c）剂量组的详细信息以及所有关于肿瘤反应和健康状况的数据通过计算机使用程序包PAPILLOM进行处理。后者是专门为此目的开发的，用APL编程语言编写，设计便于动物实验室工作人员操作。该程序包根据每个促癌剂剂量组的个体记录，计算任何一个暴露时间的累积肿瘤发生率（和生存数据）及其置信限，并且该程序包可以与用于统计验证的程序链接。此外，根据集体记录，它可以计算任何暴露时间计算肿瘤发生率、肿瘤产量和生存率。通过这两种标准方案（16或28）获得的这些数据具有完全可比性。对于纯化合物，它们可用于计算半定量的肿瘤促进效力。整理了散布在先前论文中或根据先前论文计算得出的80多种大戟烷型、瑞香烷型和芫花烷型多官能二萜的这些值及其刺激性。近年来，计算机辅助标准方案16已用于处理和评估约1000个促癌剂剂量组。方案16允许从任何一个剂量组中提取和利用更多更好的关于肿瘤反应和健康状况的毒理学信息，使用的实验动物数量明显少于方案28的要求。因此，计算机辅助标准方案16在实验数据的数量、质量和管理以及动物保护要求方面优化了小鼠皮肤实验模型的效用。
