Nicholas School of the Environment, Duke University, Durham, North Carolina.
Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States.
J Toxicol Environ Health B Crit Rev. 2021 Feb 17;24(2):51-94. doi: 10.1080/10937404.2021.1884921. Epub 2021 Feb 22.
has emerged as a major model in biomedical and environmental toxicology. Numerous papers on toxicology and pharmacology in have been published, and this species has now been adopted by investigators in academic toxicology, pharmacology, and drug discovery labs. has also attracted the interest of governmental regulatory agencies charged with evaluating the safety of chemicals. However, a major, fundamental aspect of toxicological science remains underdeveloped in : xenobiotic metabolism and transport processes that are critical to understanding toxicokinetics and toxicodynamics, and extrapolation to other species. The aim of this review was to initially briefly describe the history and trajectory of the use of in toxicological and pharmacological studies. Subsequently, physical barriers to chemical uptake and the role of the worm microbiome in xenobiotic transformation were described. Then a review of what is and is not known regarding the classic Phase I, Phase II, and Phase III processes was performed. In addition, the following were discussed (1) regulation of xenobiotic metabolism; (2) review of published toxicokinetics for specific chemicals; and (3) genetic diversity of these processes in . Finally, worm xenobiotic transport and metabolism was placed in an evolutionary context; key areas for future research highlighted; and implications for extrapolating toxicity results to other species discussed.
已经成为生物医学和环境毒理学的主要模型。大量关于毒理学和药理学的论文已经在 上发表,现在这个物种已经被学术毒理学、药理学和药物发现实验室的研究人员采用。 也引起了负责评估化学品安全性的政府监管机构的兴趣。然而,毒理学科学的一个主要的、基本的方面在 中仍然不发达:对理解毒代动力学和毒效动力学以及外推到其他物种至关重要的外源性代谢物和转运过程。本综述的目的是首先简要描述在毒理学和药理学研究中使用 的历史和轨迹。随后,描述了化学物质摄取的物理障碍和蠕虫微生物组在外源性转化中的作用。然后对关于经典 I 期、II 期和 III 期过程的已知和未知内容进行了综述。此外,还讨论了以下内容:(1) 外源性代谢物的调节;(2) 特定化学物质的已发表毒代动力学综述;以及 (3) 在 中的这些过程的遗传多样性。最后,将蠕虫外源性运输和代谢置于进化背景下;强调了未来研究的重点领域;并讨论了将 毒性结果外推到其他物种的意义。