Bailey G S, Hendricks J D, Nixon J E, Pawlowski N E
Drug Metab Rev. 1984;15(4):725-50. doi: 10.3109/03602538409041078.
Systematic design of replacement chemicals with reduced toxicities will require knowledge of mechanisms of action of parent compounds, especially in species which occupy the environment of most likely exposure. For aquatic systems, the rainbow trout has proven a valuable model for studying mechanisms of carcinogenicity. By comparison, small aquarium species show great potential as in situ field monitors of aquatic contamination by toxic chemicals but are less developed for mechanism studies. Fish species, especially rainbow trout, have also proven useful alternatives to traditional rodent models for comparative studies on mechanisms of action of nonaquatic carcinogens. These kinds of comparative studies form an essential basis for extrapolation of animal studies to man. Carcinogenicity testing of individual compounds and their replacements can provide only limited information on the expected impact of such chemicals on natural populations, since these populations are unavoidably exposed to potent modulators of the carcinogenic response. Hence any program which aims at redesign of commercial chemicals with reduced toxicities must have as a prior aim the full understanding of the mechanisms of joint carcinogen-inhibitor-promotor interactions. Because of their high sensitivity, low cost per individual, and low background tumor incidences, fish models such as the rainbow trout may be the only vertebrate models in which it is economically practical to initiate such complex studies.
系统设计毒性降低的替代化学品需要了解母体化合物的作用机制，尤其是在最有可能接触到这些化合物的环境中的物种。对于水生系统而言，虹鳟鱼已被证明是研究致癌机制的宝贵模型。相比之下，小型水族箱物种作为有毒化学物质对水生污染的原位现场监测器具有很大潜力，但在机制研究方面发展较少。鱼类物种，尤其是虹鳟鱼，也已被证明是传统啮齿动物模型的有用替代品，可用于非水生致癌物作用机制的比较研究。这类比较研究是将动物研究外推至人类的重要基础。单个化合物及其替代品的致癌性测试只能提供关于此类化学物质对自然种群预期影响的有限信息，因为这些种群不可避免地会接触到致癌反应的强效调节剂。因此，任何旨在重新设计毒性降低的商业化学品的计划，必须将充分了解联合致癌物 - 抑制剂 - 促进剂相互作用的机制作为首要目标。由于虹鳟鱼等鱼类模型具有高敏感性、个体成本低以及背景肿瘤发生率低的特点，它们可能是开展此类复杂研究在经济上可行的唯一脊椎动物模型。
