Rosenkranz H S
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, PA.
IARC Sci Publ. 1992(116):271-7.
The application of structure-activity concepts to the elucidation of the action of chemical carcinogens may proceed by two approaches: the hypothesis and the knowledge-based approaches. The former, exemplified by the 'structural alerts' devised by Ashby and associates, derives from the recognition of the electrophilic nature of carcinogens that damage DNA. The latter approach does not assume an a priori mechanism of action but derives information from the establishment of relationships between structural features and carcinogenicity. Indeed, the 'structural alerts' of Ashby et al. are recognized by such an approach; however, if structural features are associated with the activity of 'nongenotoxic' carcinogens, they would also be recognized by the knowledge-based approach. Obviously, the recognition of new (nonelectrophilic) structural features associated with carcinogenicity will lead to testable hypotheses.
假说方法和基于知识的方法。前者以阿什比及其同事设计的“结构警示”为例，源于对损伤DNA的致癌物亲电性质的认识。后一种方法并不假定一种先验的作用机制，而是从结构特征与致癌性之间关系的建立中获取信息。实际上，阿什比等人的“结构警示”就是通过这种方法识别出来的；然而，如果结构特征与“非遗传毒性”致癌物的活性相关，它们也会被基于知识的方法识别出来。显然，识别与致癌性相关的新的（非亲电的）结构特征将产生可检验的假说。
