Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, PO Box 80, Lucknow 226001, Uttar Pradesh, India.
Int J Hyg Environ Health. 2013 Aug;216(5):553-65. doi: 10.1016/j.ijheh.2013.04.001. Epub 2013 May 9.
The release of particulate pollutants into the air through burning of coal, crude oil, diesel, coal tar, etc. raises concerns of potential health hazards to the exposed human population. Polycyclic aromatic hydrocarbons (PAHs) are major toxic constituents of particulate matter (PM), which upon ingestion get metabolized to even more toxic metabolites such as quinones. The PAHs levels were assessed in both respirable particulate matter (RSPM, <10μM size) and suspended particulate matter (SPM, >10μM size) of urban ambient air (UAA) and that of major contributors viz. diesel exhaust particles (DEPs) and coal tar combustions emissions (CTCE). Seven US Environmental Protection Agency (USEPA) prioritized PAHs in RSPM and 10 in SPM were detected in UAA. Ten and 15 prioritized PAHs, respectively, were also detected in diesel exhaust particles (DEP) and coal tar combustion emission (CTCE) evidencing their release in the air. These PM associated PAHs for UAA, DEP and CTCE showed significant increase (p<0.05) in mutagenicity and mammalian genotoxicity in the order CTCE>DEP>UAA. Human lung alveolar (A549) and bronchiolar (BEAS-2B) cells when treated with PAH-metabolites viz. 1,4-benzoquinone (1,4-BQ), hydroquinone (HQ), 1,2-naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ) and 9,10-phenanthroquinone (9,10-PQ) showed metabolic modulation in these cell lines with significant depletion of principal cellular metabolites viz. NADP, uracil, asparagines, glutamine, and histidine and accumulation of di-methyl amine and beta-hydroxybutyrate, identified using (1)H NMR spectroscopy. These results suggest that PAH-quinones induce genotoxic effects by modulating the metabolic machinery inside the cells by a combined effect of oxidative stress and energy depletion. Our data for metabolic profiling of human lung cells could also help in understanding the mechanism of toxicity of other xenobiotics.
燃烧煤、原油、柴油、煤焦油等会将颗粒状污染物释放到空气中，这引起了人们对暴露于其中的人类健康潜在危害的关注。多环芳烃（PAHs）是颗粒物（PM）的主要有毒成分，这些物质进入人体后会代谢成更有毒的代谢物，如醌类。研究人员评估了城市环境空气中可吸入颗粒物（RSPM，<10μM 大小）和悬浮颗粒物（SPM，>10μM 大小）中的多环芳烃水平，以及主要污染源如柴油尾气颗粒（DEP）和煤焦油燃烧排放（CTCE）中的多环芳烃水平。在美国环境保护署（USEPA）优先评估的 7 种 RSPM 中的多环芳烃和 10 种 SPM 中的多环芳烃在 UAA 中都有检测到。在柴油尾气颗粒（DEP）和煤焦油燃烧排放（CTCE）中也分别检测到 10 种和 15 种优先多环芳烃，证明它们在空气中释放。这些与 PM 相关的 UAA、DEP 和 CTCE 中的多环芳烃的致突变性和哺乳动物遗传毒性都显著增加（p<0.05），其顺序为 CTCE>DEP>UAA。用 1,4-苯醌（1,4-BQ）、对苯二酚（HQ）、1,2-萘醌（1,2-NQ）、1,4-萘醌（1,4-NQ）和 9,10-菲醌（9,10-PQ）等 PAH 代谢物处理人肺肺泡（A549）和细支气管（BEAS-2B）细胞后，这些细胞系中的代谢发生了调节，主要细胞代谢物 NADP、尿嘧啶、天冬酰胺、谷氨酰胺和组氨酸显著减少，二甲基胺和β-羟基丁酸积累，使用（1）H NMR 光谱法鉴定。这些结果表明，PAH-醌类通过氧化应激和能量耗竭的综合作用，调节细胞内的代谢机制，诱导遗传毒性效应。我们对人肺细胞代谢谱的研究结果也有助于了解其他外源性化学物质的毒性机制。
