Xenobiotic metabolism and transport in Caenorhabditis elegans

Caenorhabditis elegans has emerged as a major model in biomedical and environmental toxicology. Numerous papers on toxicology and pharmacology in C. elegans have been published, and this species has now been adopted by investigators in academic toxicology, pharmacology, and drug discovery labs. C. elegans 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 C. elegans: 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 C. elegans 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 C. elegans. Finally, worm xenobiotic transport and metabolism was placed in an evolutionary context; key areas for future research highlighted; and implications for extrapolating C. elegans toxicity results to other species discussed.

秀丽隐杆线虫（Caenorhabditis elegans）已成为生物医学和环境毒理学领域的重要模型。关于秀丽隐杆线虫的毒理学和药理学研究，已有多篇论文发表，该物种现已被学术毒理学、药理学和药物发现实验室的研究人员所采用。秀丽隐杆线虫亦引起了负责评估化学品安全性的政府监管机构的关注。然而，在秀丽隐杆线虫中，毒理学科学的一个根本方面尚待完善：即外源物代谢和转运过程，这对于理解毒代动力学和毒效动力学，以及将其外推至其他物种至关重要。本综述的目的是首先简要介绍秀丽隐杆线虫在毒理学和药理学研究中的应用历史和轨迹。随后，描述了化学物质吸收的物理屏障以及线虫微生物群在外源物转化中的作用。接着，对经典的一期、二期和三期过程所知与未知之处进行了综述。此外，还讨论了以下内容：（1）外源物代谢的调控；（2）特定化学品的已发表毒代动力学；（3）秀丽隐杆线虫中这些过程的遗传多样性。最后，将蠕虫的外源物转运和代谢置于进化背景中；强调了未来研究的重点领域；并讨论了将秀丽隐杆线虫的毒性研究结果外推至其他物种的潜在影响。