Garry Sébastien, Nesslany Fabrice, Aliouat ElMoukhtar, Haguenoer Jean-Marie, Marzin Daniel
Laboratoire de Toxicologie Génétique, Institut Pasteur de Lille, France.
Mutat Res. 2003 Jul 8;538(1-2):19-29. doi: 10.1016/s1383-5718(03)00082-2.
Since epidemiological studies have firmly implied the co-exposition between iron oxides and polycyclic aromatic hydrocarbons (PAH) as potential etiological factor involved in the excess of mortality by lung cancer in miners, experimental studies have been performed to investigate the role of iron particles on benzo[a]pyrene (B[a]P)-induced lung pathogenesis. In the present study, the alkaline single-cell gel electrophoresis (SCGE; Comet Assay) was used to measure DNA single-strand breaks in four cell types (alveolar macrophages, lung cells, peripheral lymphocytes and hepatocytes) of OFA Sprague-Dawley rats 24h after endotracheal administration of a single dose of an iron oxide (hematite; Fe(2)O(3)) (0.75mg) or B[a]P (0.75mg) or B[a]P (0.75mg) coated onto hematite particles (0.75mg). No damage was observed in cell from the four investigated organs in rats treated with iron oxide alone, while a statistically significant increase in DNA damage was observed compared with control animals in all tested cell types of rats treated with B[a]P alone or in association with hematite. The highest levels of damage were observed in lung cells and peripheral lymphocytes; the levels of damage in alveolar macrophages and hepatocytes were increased, but to a lesser extent compared with the first two cell types. The main finding was to notice a statistically significant increase of the damage in all organs of rats treated with B[a]P coated onto hematite (approximately two-fold increases; P<0.001), versus B[a]P alone. The current study shows that iron particles increase the genotoxic properties of B[a]P in the respiratory tract of endotracheally treated OFA Sprague-Dawley rats. Hence, our data may contribute to explain the excess mortality by lung cancer in epidemiological studies and overall why exposures to B[a]P coated onto Fe(2)O(3) particles resulted in higher toxicity in rodents compared with exposure to B[a]P alone.
由于流行病学研究已明确表明，氧化铁与多环芳烃（PAH）的共同暴露可能是导致矿工肺癌死亡率过高的潜在病因，因此开展了实验研究，以探究铁颗粒在苯并[a]芘（B[a]P）诱发的肺部病变中的作用。在本研究中，采用碱性单细胞凝胶电泳（SCGE；彗星试验）来检测经气管内单次给予单剂量氧化铁（赤铁矿；Fe(2)O(3)）（0.75毫克）或B[a]P（0.75毫克）或包裹在赤铁矿颗粒（0.75毫克）上的B[a]P（0.75毫克）24小时后，OFA斯普拉格-道利大鼠四种细胞类型（肺泡巨噬细胞、肺细胞、外周淋巴细胞和肝细胞）中的DNA单链断裂情况。单独用氧化铁处理的大鼠，其四个被研究器官的细胞未观察到损伤，而单独用B[a]P处理或与赤铁矿联合处理的大鼠，所有测试细胞类型与对照动物相比，DNA损伤均有统计学意义的增加。肺细胞和外周淋巴细胞中的损伤水平最高；肺泡巨噬细胞和肝细胞中的损伤水平有所增加，但与前两种细胞类型相比程度较小。主要发现是，与单独使用B[a]P相比，用包裹在赤铁矿上的B[a]P处理的大鼠所有器官的损伤有统计学意义的显著增加（约增加两倍；P<0.001）。当前研究表明，铁颗粒可增强经气管内处理的OFA斯普拉格-道利大鼠呼吸道中B[a]P的遗传毒性。因此，我们的数据可能有助于解释流行病学研究中肺癌死亡率过高的现象，以及总体上为何与单独暴露于B[a]P相比，暴露于包裹在Fe(2)O(3)颗粒上的B[a]P会导致啮齿动物产生更高的毒性。
