Schirmer Kristin
Department of Cell Toxicology (CellTox), UFZ-Centre for Environmental Research Leipzig-Halle in the Helmholtz Association, Permoserstr. 15, 04318 Leipzig, Germany.
Toxicology. 2006 Jul 25;224(3):163-83. doi: 10.1016/j.tox.2006.04.042. Epub 2006 May 2.
Cultures of vertebrate cells are widely applied in mechanistic studies in human toxicology as well as in toxicity identification in ecotoxicology. As in vitro models, they display many advantages over whole animal experimentation, pertaining to such characteristics as availability, reproducibility and costs. As well, they satisfy the societal desire to reduce the number of animals in toxicology. For these reasons vertebrate cell models also appear to be a desirable replacement for animals in regulatory tests. Several vertebrate cell models are now accepted for regulatory purposes in human health sciences, with the test for photocytotoxicity using the 3T3 mouse cell line being one example. However, an in vitro alternative to whole animal tests has not yet been established for regulatory risk assessment in ecotoxicology. This review sets out to outline why such a replacement has not yet been possible and explores avenues to improve vertebrate cell cultures so that a replacement of whole animal tests could more likely be achieved. Inasmuch as fish is the most widely used non-mammalian vertebrate in risk assessment and regulation, focus will be on the replacement, by in vitro vertebrate models, of fish.
脊椎动物细胞培养在人类毒理学的机制研究以及生态毒理学的毒性鉴定中得到了广泛应用。作为体外模型,它们相对于整体动物实验具有许多优势,涉及可用性、可重复性和成本等特征。此外,它们满足了社会减少毒理学中动物数量的愿望。出于这些原因,脊椎动物细胞模型似乎也是监管测试中替代动物的理想选择。目前,几种脊椎动物细胞模型已被人类健康科学监管目的所接受,使用3T3小鼠细胞系进行光细胞毒性测试就是一个例子。然而,生态毒理学的监管风险评估尚未建立起替代整体动物测试的体外方法。本综述旨在概述为何尚未实现这种替代,并探索改进脊椎动物细胞培养的途径,以便更有可能实现对整体动物测试的替代。鉴于鱼类是风险评估和监管中使用最广泛的非哺乳动物脊椎动物,重点将放在体外脊椎动物模型对鱼类的替代上。