Mougabure-Cueto G, Sfara V
Centro de Referencia de Vectores (Ce.Re.Ve.), Ministerio de Salud de la Nación Argentina, Hospital Colonia Pabellón Rawson calle s/n (5164), Santa María de Punilla, Córdoba, Argentina.
Instituo de Investigación e Ingeniería Ambiental, Universidad Nacional de San Martín (3iA-UNSAM), 25 de Mayo y Francia (1650), San Martín, Buenos Aires, Argentina.
Toxicol Lett. 2016 Apr 25;248:46-51. doi: 10.1016/j.toxlet.2016.03.001. Epub 2016 Mar 4.
Dose-response relations can be obtained from systems at any structural level of biological matter, from the molecular to the organismic level. There are two types of approaches for analyzing dose-response curves: a deterministic approach, based on the law of mass action, and a statistical approach, based on the assumed probabilities distribution of phenotypic characters. Models based on the law of mass action have been proposed to analyze dose-response relations across the entire range of biological systems. The purpose of this paper is to discuss the principles that determine the dose-response relations. Dose-response curves of simple systems are the result of chemical interactions between reacting molecules, and therefore are supported by the law of mass action. In consequence, the shape of these curves is perfectly sustained by physicochemical features. However, dose-response curves of bioassays with quantal response are not explained by the simple collision of molecules but by phenotypic variations among individuals and can be interpreted as individual tolerances. The expression of tolerance is the result of many genetic and environmental factors and thus can be considered a random variable. In consequence, the shape of its associated dose-response curve has no physicochemical bearings; instead, they are originated from random biological variations. Due to the randomness of tolerance there is no reason to use deterministic equations for its analysis; on the contrary, statistical models are the appropriate tools for analyzing these dose-response relations.
剂量-反应关系可以从生物物质的任何结构层次的系统中获得，从分子水平到机体水平。分析剂量-反应曲线有两种方法：一种是基于质量作用定律的确定性方法，另一种是基于表型特征假定概率分布的统计方法。已经提出了基于质量作用定律的模型来分析整个生物系统范围内的剂量-反应关系。本文的目的是讨论决定剂量-反应关系的原理。简单系统的剂量-反应曲线是反应分子之间化学相互作用的结果，因此得到质量作用定律的支持。因此，这些曲线的形状完全由物理化学特征维持。然而，具有定量反应的生物测定的剂量-反应曲线不是由分子的简单碰撞来解释的，而是由个体之间的表型变异来解释的，并且可以被解释为个体耐受性。耐受性的表达是许多遗传和环境因素的结果，因此可以被认为是一个随机变量。因此，其相关剂量-反应曲线的形状没有物理化学依据；相反，它们源于随机的生物学变异。由于耐受性的随机性，没有理由使用确定性方程对其进行分析；相反，统计模型是分析这些剂量-反应关系的合适工具。
