Lutz W K
Department of Toxicology, University of Wuerzburg, Germany.
Hum Exp Toxicol. 2000 Oct;19(10):566-8; discussion 571-2. doi: 10.1191/096032700701546488.
Strongly sigmoidal (S-shaped) dose-cancer incidence relationships are often observed in animal bioassays for carcinogenicity. If a genotoxic contribution is not plausible, an epigenetic mode of carcinogen action is proposed and a thresholded low dose-response suggested. In a strict sense, a threshold implies a no-yes situation, i.e., no effect up to the threshold dose and an effect above the threshold dose. A convincing explanation of the discontinuity of the gradient of the dose-response curve at the threshold dose is not available to me. However, the existence of a threshold is accepted for an individual. The threshold dose is the dose required for the manifestation of the tumor in an individual exactly at the end of a defined period of observation (for instance, 2 years in an animal bioassay, 75 years in humans). Because of genetic and lifestyle-dependent susceptibility differences, each animal or human has his individual threshold dose. For a group, no single threshold dose can be defined, irrespective of the mode of carcinogen action. Furthermore, in view of the stochastic elements in the process of carcinogenesis, the exact threshold dose can only be defined after tumor incidence and cannot be predicted.
在动物致癌性生物测定中，经常观察到强S形（Sigmoid形）剂量-癌症发生率关系。如果遗传毒性作用不太可能，就会提出致癌物作用的表观遗传模式，并提出有阈值的低剂量反应。严格来说，阈值意味着一种非此即彼的情况，即低于阈值剂量无效应，高于阈值剂量则有效应。我无法对阈值剂量处剂量反应曲线梯度的不连续性给出令人信服的解释。然而，个体的阈值是被认可的。阈值剂量是指在特定观察期结束时（例如，动物生物测定中为2年，人类中为75年）个体恰好出现肿瘤所需的剂量。由于遗传和生活方式导致的易感性差异，每只动物或每个人都有其个体阈值剂量。对于一个群体而言，无论致癌物作用模式如何，都无法定义单一的阈值剂量。此外，鉴于致癌过程中的随机因素，确切的阈值剂量只能在肿瘤发生率出现后才能确定，无法进行预测。
