Johnson E M, Gorman R M, Gabel B E, George M E
Teratog Carcinog Mutagen. 1982;2(3-4):263-76. doi: 10.1002/1520-6866(1990)2:3/4<263::aid-tcm1770020308>3.0.co;2-i.
By a uniformly applied protocol, adult hydra are exposed to a test substance over a broad range of concentrations, and the minimal toxic concentration is determined to within one-tenth log. In a second experiment, dissociated hydra cells are manipulated into a configuration wherein, if undisturbed, they will achieve the developmental events characteristic of any embryo and undergo total whole-body regeneration. During its 4-day ontogenesis this artificial "embryo" is exposed to the test substance by the same protocol as the adult and the minimal developmentally toxic concentration is determined to within one-tenth log. The ratio of the adult (A) to the developmentally (D) toxic concentration is calculated. A small A/D ratio indicates that the substance disrupts development only at or near the concentration also toxic to the adult (a developmentally nonhazardous substance or coeffective teratogen). A large A/D ratio indicates that a substance disrupts developmental events at a small fraction of the exposure toxic to adults (a developmental hazard). The system is directly predictable of a putative teratogen's hazard potential (A/D ratio) in standard laboratory animals and man. It provides an objective and reliable means to prioritize otherwise untested substances according to the need for further study of their developmental toxicity.
通过统一应用的方案,将成年水螅暴露于广泛浓度范围的测试物质中,并将最小毒性浓度精确到十分之一对数范围内。在第二个实验中,将解离的水螅细胞处理成一种结构,在不受干扰的情况下,它们将经历任何胚胎特有的发育过程并实现全身完全再生。在这个人工“胚胎”4天的个体发育过程中,按照与成年水螅相同的方案将其暴露于测试物质中,并将最小发育毒性浓度精确到十分之一对数范围内。计算成年水螅的毒性浓度(A)与发育毒性浓度(D)的比值。较小的A/D比值表明该物质仅在对成年水螅有毒的浓度或接近该浓度时才会干扰发育(一种发育无危害物质或协同效应致畸剂)。较大的A/D比值表明该物质在对成年水螅有毒的暴露浓度的一小部分时就会干扰发育事件(一种发育危害)。该系统可以直接预测标准实验动物和人类中推定致畸剂的危害潜力(A/D比值)。它提供了一种客观可靠的方法,可根据对其发育毒性进行进一步研究的需要,对其他未经测试的物质进行优先级排序。