Combustion products of 1,3-butadiene are cytotoxic and genotoxic to human bronchial epithelial cells

Adverse health effects of airborne toxicants, especially small respirable p articles 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 south ern California) chronically have poor air quality. Atmospheric releases of products of incomplete combustion (e.g., soot) from these facilities are no t subject to rigorous regulatory enforcement. Although soot can include res pirable particles and carcinogens, the toxicologic and epidemiologic conseq uences of exposure to environmentally relevant complex soots have not been well investigated. Here we continue our physico-chemical analysis of butadi ene soot and report effects of exposure to this soot on putative targets, n ormal human bronchial epithelial (NHBE) cells. We examined organic extracts of butadiene soot by gas chromatography-mass spectrometry (GC-MS), probe d istillation MS, and liquid chromatography (LC)-MS-MS. Hundreds of aromatic hydrocarbons and polycyclic aromatic hydrocarbons with molecular mass as hi gh 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 anal ysis. Spin-trapping studies indicated that fresh butadiene soot in a buffer ed aqueous solution containing dimethylsulfoxide (DMSO) oxidized the DMSO, leading to CH3. radical formation. Butadiene soot DMSO extract (BSDE)-expos ed 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-i nduced form of cell death. BSDE treatment also produced significant genotox icity, as indicated by binucleated cell formation. The combination of moder ate cytotoxicity and genotoxicity, as occurred here, can be pro-carcinogeni c.