Ambient particulate matter induces oxidative DNA damage in lung epithelial cells
Ambient particulate matter induces oxidative DNA damage in lung epithelial cells
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DOI：
10.1080/08958378.2000.11463238
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发表时间：
2000-01-01
影响因子：
2.1
通讯作者：
Borm, PJA
中科院分区：
文献类型：
--
作者：
Knaapen, AM;Schins, RPF;Borm, PJA
虽然流行病学研究已经确定了PM10水平与急性心血管和呼吸系统并发症之间的相关性，但几乎没有任何关于可能的慢性影响（如癌症）的数据。本研究的目的是调查由环境颗粒物（TSP）产生的自由基，并将这些数据与肺上皮细胞中的氧化DNA损伤联系起来。与先前在PM10中的发现一致，超螺旋质粒DNA被TSP以及TSP上清液耗尽（p <0.001），并且在甘露醇（5 mM）存在下，这种作用降低。利用电子自旋共振（ESR）和自旋陷阱二甲基-1-吡咯啉N-氧化物（DMPO），我们能够表明，羟基自由基（（OH）-O-。）由TSP和TSP上清液形成。当TSP与去铁胺（5 mM）预孵育时，DMPO-OH信号完全消失，表明铁和其他可溶性金属在此过程中的重要性。TSP上清液的原子吸收光谱（AAS）分析表明存在可溶性Fe、V和Ni（分别为253.0、14.7和76.0 μ g/g不溶性TSP）。探讨（OH）-O-的生物学意义。通过免疫细胞化学在大鼠II型细胞系中测量TSP 8-羟基脱氧鸟苷（8-oxodG）的形成。与TSP上清液孵育后，羟自由基特异性DNA加合物的形成增加了两倍（p <0.01），去铁胺可抑制这种作用（p <0.01）。
Although epidemiological studies have established a correlation between PM10 levels and acute cardiovascular and respiratory complications, hardly any data is available on possible chronic effects such as cancer. The purpose of this study was to investigate the production of free radicals by ambient particulate matter (TSP) and to link these data to oxidative DNA damage in lung epithelial cells. In line with previous findings oil PM10, supercoiled plasmid DNA was depleted by TSP as well as TSP supernatant (p < .001) and this effect was reduced in the presence of mannitol (5 mM). Using electron spin resonance (ESR) and the spin trap dimethyl-1-pyrroline N-oxide (DMPO) we were able to show that hydroxyl radicals ((OH)-O-.) are formed from both TSP and TSP supernatant. The DMPO-OH signal was completely abrogated when TSP was preincubated with deferoxamine (5 mM), showing the importance of iron and other soluble metals in this process. Atomic absorption spectroscopy (AAS) analysis of the TSP supernatant showed the presence of soluble Fe, V: and Ni (respectively 253.0, 14.7, and 76.0 mu g/g insoluble TSP). To investigate the biological significance of (OH)-O-. formation by TSP 8-hydroxydeoxyguanosine (8-oxodG) was measured in a rat type II cell line by immunocytochemistry. The formation of ih is hydroxyl-radical-specific DNA adduct was increased twofold (p < .01) after incubation with TSP supernatants, and this effect was inhibited by deferoxamine (p