King's College London, Faculty of Life Sciences and Medicine, Analytical, Environmental and Forensic Sciences Department, London, SE1 9NH, UK.
InVivo Biosystems, Eugene, OR, 97402, USA.
Environ Pollut. 2023 Dec 15;339:122731. doi: 10.1016/j.envpol.2023.122731. Epub 2023 Oct 13.
Polycyclic aromatic hydrocarbons (PAHs), in particular benzo [a]pyrene (BaP), have been identified as carcinogenic components of tobacco smoke. In mammals, the toxicological response to BaP-diol-epoxide is driven by cytochrome P450 (CYP1A1), a pathway which is absent in Caenorhabditis elegans. In contrast, in worms prominently the CYP-35 enzyme family seems to be induced after BaP exposure. In C. elegans, BaP exposure reduces the accumulation of lysosomal neutral lipids in a dose dependent manner and the deletion of cyp-35A2 results in a significant elevation of neutral lipid metabolism. A cyp-35A2:mCherry;unc-47:GFP dual-labelled reporter strain facilitated the identification of three potential upstream regulators that drive BaP metabolism in worms, namely elt-2, nhr-49 and fos-1. This newly described reporter line is a powerful resource for future large-scale RNAi regarding toxicology and lipid metabolism screens.
多环芳烃（PAHs），特别是苯并[a]芘（BaP），已被确定为烟草烟雾中的致癌成分。在哺乳动物中，BaP-二醇-环氧化物的毒理学反应是由细胞色素 P450（CYP1A1）驱动的，而该途径在秀丽隐杆线虫中不存在。相比之下，在蠕虫中，CYP-35 酶家族在 BaP 暴露后似乎明显被诱导。在秀丽隐杆线虫中，BaP 暴露以剂量依赖的方式减少溶酶体中性脂质的积累，而 cyp-35A2 的缺失导致中性脂质代谢显著升高。cyp-35A2:mCherry;unc-47:GFP 双标记报告株有助于鉴定三种潜在的上游调节剂，它们驱动蠕虫中的 BaP 代谢，即 elt-2、nhr-49 和 fos-1。这条新描述的报告线是未来进行大规模 RNAi 毒理学和脂质代谢筛选的强大资源。
