Defining the transcriptomic fingerprints of benzo[a]pyrene exposure in Caenorhabditis elegans. Defining the transcriptomic fingerprints of benzo[a]pyrene exposure in Caenorhabditis elegans

Polycyclic aromatic hydrocarbons (PAHs) are abundant organic compounds and are anthropogenically produced by the incomplete combustion of organic matter (e.g. fossil fuels and tobacco smoke). One notable model PAH is benzo[a]pyrene (BaP), which is listed as a Group 1 human carcinogen by the International Agency of Research on Cancer (IARC). Although the mode of action for BaP is well known in higher organisms, limited knowledge is available regarding the consequence of BaP exposure in the model organism Caenorhabditis elegans. The objective of this study was to define the the global transcriptome of wild-type C. elegans exposed to BaP (0, 5 and 20 μM). The most responsive transcripts were linked to redox processes and xenobiotic responses, including P450 enzymes (CYPs) (mainly members of the CYP35 family), epoxide hydrolases (EHs), glutathione S-transferases (GSTs), and UDP-glucuronosyltransferases (UGTs), all of which are linked to the metabolism (phase I & II) of xenobiotic substances. In summary, although the dominant CYP1A1/2 & CYP1B1 metabolic pathway is absent in C. elegans, BaP still induced a strong transcriptomic response. This provides strong evidence that parallel pathway(s) are implicated in BaP metabolism, and possibly, in its detoxification. Overall design: The global transcriptome was compared in wild type N2 raised in the presence or absence of benzo[a]pyrene at the concentration of 0,5 or 20 μM for for 48 hours from L1 stage to L4 stage.

多环芳烃（Polycyclic Aromatic Hydrocarbons, PAHs）是一类分布广泛的有机化合物，可通过有机物不完全燃烧人为产生（如化石燃料、烟草烟雾）。典型的模式多环芳烃为苯并[a]芘（benzo[a]pyrene, BaP），其已被国际癌症研究机构（International Agency for Research on Cancer, IARC）列为一类人类致癌物。尽管BaP的作用机制在高等生物中已得到充分阐明，但目前关于模式生物秀丽隐杆线虫（Caenorhabditis elegans）暴露于BaP后的影响的相关认知仍较为有限。本研究旨在明确暴露于0、5和20 μM BaP的野生型秀丽隐杆线虫的全局转录组特征。响应最为显著的转录本与氧化还原过程及异源物质应答相关，包括细胞色素P450酶（P450 enzymes, CYPs，主要为CYP35家族成员）、环氧水解酶（epoxide hydrolases, EHs）、谷胱甘肽S-转移酶（glutathione S-transferases, GSTs）以及UDP-葡萄糖醛酸转移酶（UDP-glucuronosyltransferases, UGTs），上述酶类均与异源物质的I相及II相代谢密切相关。综上，尽管秀丽隐杆线虫中不存在经典的CYP1A1/2及CYP1B1代谢通路，但BaP仍可诱导强烈的转录组应答。该结果为平行代谢通路参与BaP代谢（或其解毒过程）提供了有力证据。总体实验设计：将从L1期培养至L4期的野生型N2线虫，分别置于含0、5或20 μM苯并[a]芘的培养基中培养48小时，随后对其全局转录组进行比较分析。