Combustion Products of 1,3-Butadiene Are Cytotoxic and Genotoxic to Human Bronchial Epithelial Cells. (Articles)

Article excerpt

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 C[H.sub.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. Key words: blebbing, BSDE, butadiene soot, fluorescence, free radicals, human bronchial epithelial cells, PAHs. Environ Health Perspect 109:965-971 (2001). [Online 12 September 2001]


Cardiovascular disease and lung cancer are among the leading causes of death both in Louisiana and throughout the rest of the United States. Age-adjusted death rates are higher in Louisiana than in the rest of the country for both groups of diseases (1). Additionally, the death rate from chronic obstructive pulmonary disease is 58% higher in Louisiana than the national average (2).

Increasingly, researchers have focused on airborne particles as causes of respiratory (and more recently, in cardiovascular) disease. Adsorbed organic compounds have been implicated in many of the systemic and molecular responses of respiratory system cells exposed to diesel exhaust particles (3-6). Studies with residual oil fly ash (ROFA) particles have demonstrated a role for particle-associated metals in inducing inflammatory responses in respiratory cells (7,8).

Epidemiologic evidence from the past decade has correlated increased respiratory morbidity and mortality with exposures to small airborne particles. National Ambient Air Quality Standards issued by the U.S. Environmental Protection Agency in 1997 (9), shifting the focus from larger particles ([less than or equal to] 10 [micro]m) to those [less than or equal to] 2.5 [micro]m (so called P[M.sub.2.5]), reflect this.

Among the most common origins of airborne particles, industrial point sources [i.e., major facilities, each emitting [less than or equal to] 10 tons/yr of specific hazardous air pollutants (HAPs) or [less than or equal to] 25 tons/yr of a mixture of HAPs] are of particular concern in Louisiana. …