Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway.
Toxicol Appl Pharmacol. 2010 Feb 1;242(3):270-80. doi: 10.1016/j.taap.2009.10.017. Epub 2009 Oct 29.
Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are found in diesel exhaust and air pollution particles. Along with other PAHs, many nitro-PAHs possess mutagenic and carcinogenic properties, but their effects on pro-inflammatory processes and cell death are less known. In the present study we examined the effects of 1-nitropyrene (1-NP), 3-nitrofluoranthene (3-NF) and 3-nitrobenzanthrone (3-NBA) and their corresponding amino forms, 1-AP, 3-AF and 3-ABA, in human bronchial epithelial BEAS-2B cells. The effects of the different nitro- and amino-PAHs were compared to the well-characterized PAH benzo[a]pyrene (B[a]P). Expression of 17 cytokine and chemokine genes, measured by real-time PCR, showed that 1-NP and 3-NF induced a completely different cytokine/chemokine gene expression pattern to that of their amino analogues. 1-NP/3-NF-induced responses were dominated by maximum effects on CXCL8 (IL-8) and TNF-alpha expression, while 1-AP-/3-AF-induced responses were dominated by CCL5 (RANTES) and CXCL10 (IP-10) expression. 3-NBA and 3-ABA induced only marginal cytokine/chemokine responses. However, 3-NBA exposure induced considerable DNA damage resulting in accumulation of cells in S-phase and a marked increase in apoptosis. B[a]P was the only compound to induce expression of aryl hydrocarbon receptor (AhR)-regulated genes, such as CYP1A1 and CYP1B1, but did not induce cytokine/chemokine responses in BEAS-2B cells. Importantly, nitro-PAHs and amino-PAHs induced both qualitatively and quantitatively different effects on cytokine/chemokine expression, DNA damage, cell cycle alterations and cytotoxicity. The cytokine/chemokine responses appeared to be triggered, at least partly, through mechanisms separate from the other examined endpoints. These results confirm and extend previous studies indicating that certain nitro-PAHs have a considerable pro-inflammatory potential.
硝基多环芳烃（Nitro-PAHs）存在于柴油废气和空气污染颗粒中。与其他多环芳烃一样，许多硝基-PAH 具有致突变性和致癌性，但它们对促炎过程和细胞死亡的影响知之甚少。在本研究中，我们研究了 1-硝基芘（1-NP）、3-硝基荧蒽（3-NF）和 3-硝基苯并蒽（3-NBA）及其相应的氨基形式 1-AP、3-AF 和 3-ABA 在人支气管上皮 BEAS-2B 细胞中的作用。不同的硝基和氨基 PAH 的作用与特征明确的 PAH 苯并[a]芘（B[a]P）进行了比较。通过实时 PCR 测量的 17 种细胞因子和趋化因子基因的表达表明，1-NP 和 3-NF 诱导的细胞因子/趋化因子基因表达模式与它们的氨基类似物完全不同。1-NP/3-NF 诱导的反应以最大程度地诱导 CXCL8（IL-8）和 TNF-α表达为主，而 1-AP-/3-AF 诱导的反应以 CCL5（RANTES）和 CXCL10（IP-10）表达为主。3-NBA 和 3-ABA 仅诱导微小的细胞因子/趋化因子反应。然而，3-NBA 暴露会导致相当大的 DNA 损伤，导致 S 期细胞积累，并显著增加细胞凋亡。B[a]P 是唯一诱导芳香烃受体（AhR）调节基因（如 CYP1A1 和 CYP1B1）表达的化合物，但不会诱导 BEAS-2B 细胞中的细胞因子/趋化因子反应。重要的是，硝基-PAH 和氨基-PAH 对细胞因子/趋化因子表达、DNA 损伤、细胞周期改变和细胞毒性产生了定性和定量上不同的影响。细胞因子/趋化因子反应似乎至少部分通过与其他检测终点不同的机制触发。这些结果证实并扩展了先前的研究结果，表明某些硝基-PAH 具有相当大的促炎潜力。
