Kolbye A C
Oncology. 1976;33(2):90-100. doi: 10.1159/000225113.
Cancer causation in humans is at least a three-dimensional problem too often viewed from only two dimensions, especially as far as the two-dimensional results (dose versus response) of cancer induction tests in animals are viewed. The expression of a cancer represents a critical convergence of additional factors in the third dimension which include metabolic variables, many of which may involve secondary mechanisms. Many of these mechanisms are involved in the causation pattern of cancer in humans and can be expected to operate within the dose-response considerations observed in the fields of toxicology and pharmacology. The expression of critical reactions of cells in relatively unprotected tissues may occur more readily after exposures involving fewer molecules of one "carcinogen" as compared to another "carcinogen". Results from animal tests may have limited human relevance in some instances and detract us from consideration of the more fundamental factors involved in the etiology of human cancer. A precipitous rush to "zero tolerances" for all animal carcinogens may impair our efforts to prevent the worst "causes" of cancer induction in humans.
人类癌症的成因至少是一个三维问题，但人们常常只从两个维度去看待它，尤其是在看待动物致癌试验的二维结果（剂量与反应）时。癌症的表现代表了第三维度中其他因素的关键汇聚，这些因素包括代谢变量，其中许多可能涉及次要机制。这些机制中的许多都与人类癌症的病因模式有关，并且可以预期它们会在毒理学和药理学领域所观察到的剂量反应考量范围内发挥作用。与另一种“致癌物”相比，在涉及较少分子的一种“致癌物”暴露后，相对未受保护组织中的细胞关键反应可能更容易发生。在某些情况下，动物试验的结果与人类的相关性可能有限，并且会使我们忽略对人类癌症病因中更基本因素的考虑。急于对所有动物致癌物设定“零容忍”可能会损害我们预防人类癌症最严重“病因”的努力。
