Portier C J, Edler L
Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1990 Apr;14(3):444-60. doi: 10.1016/0272-0590(90)90249-j.
The implications of a clonal two-stage model of carcinogenesis on the design and analysis of 2-year in vivo tumorigenesis experiments are addressed. Using a simple classification scheme for labelling test agents as initiators, promoters, and completers, it is shown that the standard experimental design has very little ability to differentiate between these different modes of action. Even when chemicals in one class (e.g., promoters) follow a highly nonlinear dose-response relationship and chemicals in another class (e.g., initiators) follow a linear dose-response relationship, it is difficult to reject one mode of action versus the other. A simple modification of the design using age-dependent dosing schemes produces patterns of tumor incidence which are unique to the particular class, making it slightly easier to differentiate between the assumed mechanisms of action. The implications of this finding on study design are discussed.
本文探讨了致癌作用的克隆两阶段模型对两年体内肿瘤发生实验设计和分析的影响。使用一种简单的分类方案将测试剂标记为引发剂、促进剂和完成剂，结果表明标准实验设计区分这些不同作用模式的能力非常有限。即使一类化学物质（如促进剂）遵循高度非线性的剂量反应关系，而另一类化学物质（如引发剂）遵循线性剂量反应关系，也很难拒绝一种作用模式而支持另一种。使用与年龄相关的给药方案对设计进行简单修改会产生特定类别的独特肿瘤发生率模式，从而更容易区分假定的作用机制。本文讨论了这一发现对研究设计的影响。
