Catallo W J, Kennedy C H, Henk W, Barker S A, Grace S C, Penn A
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Environ Health Perspect. 2001 Sep;109(9):965-71. doi: 10.1289/ehp.01109965.
Adverse health effects of airborne toxicants, especially small respirable particles and their associated adsorbed chemicals, are of growing concern to health professionals, governmental agencies, and the general public. Areas rich in petrochemical processing facilities (e.g., eastern Texas and southern California) chronically have poor air quality. Atmospheric releases of products of incomplete combustion (e.g., soot) from these facilities are not subject to rigorous regulatory enforcement. Although soot can include respirable particles and carcinogens, the toxicologic and epidemiologic consequences of exposure to environmentally relevant complex soots have not been well investigated. Here we continue our physico-chemical analysis of butadiene soot and report effects of exposure to this soot on putative targets, normal human bronchial epithelial (NHBE) cells. We examined organic extracts of butadiene soot by gas chromatography-mass spectrometry (GC-MS), probe distillation MS, and liquid chromatography (LC)-MS-MS. Hundreds of aromatic hydrocarbons and polycyclic aromatic hydrocarbons with molecular mass as high as 1,000 atomic mass units were detected, including known and suspected human carcinogens (e.g., benzo(a)pyrene). Butadiene soot particles also had strong, solid-state free-radical character in electron spin resonance analysis. Spin-trapping studies indicated that fresh butadiene soot in a buffered aqueous solution containing dimethylsulfoxide (DMSO) oxidized the DMSO, leading to CH(3)* radical formation. Butadiene soot DMSO extract (BSDE)-exposed NHBE cells displayed extranuclear fluorescence within 4 hr of exposure. BSDE was cytotoxic to > 20% of the cells at 72 hr. Morphologic alterations, including cell swelling and membrane blebbing, were apparent within 24 hr of exposure. These alterations are characteristic of oncosis, an ischemia-induced form of cell death. BSDE treatment also produced significant genotoxicity, as indicated by binucleated cell formation. The combination of moderate cytotoxicity and genotoxicity, as occurred here, can be pro-carcinogenic.
空气中的有毒物质，尤其是可吸入的小颗粒及其吸附的相关化学物质，对健康专业人员、政府机构和公众的健康影响日益受到关注。石化加工设施丰富的地区（如得克萨斯州东部和加利福尼亚州南部）空气质量长期较差。这些设施不完全燃烧产物（如煤烟）的大气排放未受到严格的监管执法。尽管煤烟可包括可吸入颗粒和致癌物，但接触环境相关复杂煤烟的毒理学和流行病学后果尚未得到充分研究。在此，我们继续对丁二烯煤烟进行物理化学分析，并报告接触这种煤烟对假定靶标——正常人支气管上皮（NHBE）细胞的影响。我们通过气相色谱 - 质谱联用（GC - MS）、探针蒸馏质谱和液相色谱（LC） - MS - MS对丁二烯煤烟的有机提取物进行了检测。检测到数百种分子量高达1000原子质量单位的芳烃和多环芳烃，包括已知和疑似人类致癌物（如苯并(a)芘）。在电子自旋共振分析中，丁二烯煤烟颗粒还具有很强的固态自由基特征。自旋捕获研究表明，在含有二甲基亚砜（DMSO）的缓冲水溶液中的新鲜丁二烯煤烟会氧化DMSO，导致形成CH(3)*自由基。暴露于丁二烯煤烟DMSO提取物（BSDE）的NHBE细胞在暴露4小时内就出现核外荧光。在72小时时，BSDE对超过20%的细胞具有细胞毒性。形态学改变，包括细胞肿胀和细胞膜起泡，在暴露24小时内就很明显。这些改变是胀亡的特征，胀亡是一种由缺血诱导的细胞死亡形式。如双核细胞形成所示，BSDE处理还产生了显著的遗传毒性。此处出现的中等细胞毒性和遗传毒性相结合可能具有促癌作用。
