Comparative toxicity analysis of benzo[a]pyrene and PAH4 on HepG2 cells using transcriptomics and metabolomics

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-04-23 DOI:10.1016/j.fct.2025.115473

Miao Yang , Jialin Sun , Xin Cao , Hongjuan Liu , Xudong Wu , Weifeng Mao , Liping Hao

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Abstract

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants posing potential health risks. PAH4 (sum of benzo[a]pyrene (BaP), chrysene, benz[a]anthracene and benzo[b]fluoranthene) has been proposed as a marker to evaluate the occurrence of total PAHs. However, toxicity effects of exposure to PAH4 mixture and its toxicity differences with single PAH are little-known. Here, we systematically investigated the hepatotoxicity mechanisms of PAH4 and compare its toxicity with BaP using HepG2 cell model. Our results showed that BaP and PAH4 exposure induced cytotoxicity and oxidative stress. Furthermore, both BaP and PAH4 activated P53 signaling pathway, leading to cell apoptosis, and disrupted peroxisome proliferator-activated receptor (PPAR) signaling and induced lipid metabolism disorder. Integrated analysis of transcriptomics and metabolomics indicated that BaP and PAH4 shared similar toxicity mechanisms, commonly affecting the metabolic pathways including glycerolipid and glycerophospholipid metabolism. Moreover, the integrated biomarker response (IBR) analysis demonstrated that BaP and PAH4 exhibited similar global toxicity on HepG2 cells. We further found that the toxicity effects of PAH4 could be partially alleviated by an aryl hydrocarbon receptor (AHR) antagonist, indicating a potential role of AHR signaling in PAH4-induced hepatotoxicity. Overall, these findings provided insights into the toxicological mechanisms and interaction effects of PAHs mixtures.

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利用转录组学和代谢组学分析苯并[a]芘和PAH4对HepG2细胞的毒性比较

多环芳烃（PAHs）是普遍存在的环境污染物，具有潜在的健康风险。PAH4（苯并[a]芘（BaP）、芘、苯并[a]蒽和苯并[b]荧光蒽的总和）已被提出作为评价总多环芳烃发生的标志物。然而，多环芳烃混合物暴露的毒性作用及其与单一多环芳烃的毒性差异尚不清楚。本研究采用HepG2细胞模型，系统研究了PAH4的肝毒性机制，并与BaP进行了毒性比较。我们的研究结果表明，BaP和PAH4暴露诱导细胞毒性和氧化应激。此外，BaP和PAH4均激活P53信号通路，导致细胞凋亡，并破坏过氧化物酶体增殖激活受体（PPAR）信号通路，诱导脂质代谢紊乱。转录组学和代谢组学的综合分析表明，BaP和PAH4具有相似的毒性机制，共同影响包括甘油脂和甘油磷脂代谢在内的代谢途径。此外，综合生物标志物反应（IBR）分析表明，BaP和PAH4对HepG2细胞具有相似的整体毒性。我们进一步发现芳烃受体（AHR）拮抗剂可以部分减轻PAH4的毒性作用，这表明AHR信号通路在PAH4诱导的肝毒性中可能起作用。总的来说，这些发现为多环芳烃混合物的毒理学机制和相互作用提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.