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

Abstract

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.

Combustion products of 1,3-butadiene inhibit catalase activity and induce expression of oxidative DNA damage repair enzymes in human bronchial epithelial cells

“…Previously, we reported that extranuclear fluorescence was detected within 4 h after exposure of NHBE cells to BSDE and that the fluorescence intensified up to 24 h (Catallo et al 2001). In order to establish that BSEE also causes extranuclear fluorescence, BEAS-2B cells exposed to either a vehicle control (DMSO or EtOH) or toxicant mixture (BSDE or BSEE) were visualized 6, 24, 48, and 72 h after exposure.…”

“…Based on the oxidizing potential of BDS (Catallo et al 2001), we believed that these particles would oxidize proteins in cells. If this is the case, then BDS would be expected to inhibit the activity of enzymes.…”

“…In this study, we examined intracellular fluorescence induced by butadiene soot DMSO extract (BSDE) or butadiene soot ethanol extract (BSEE) in BEAS-2B cells, an immortalized nontumorigenic human brochial epithelial cell line (Reddel et al 1988), to determine whether BSEE induces extranuclear fluorescence in the same manner as that seen previously with BSDE (Catallo et al 2001). Therefore, the oxidizing potential of BDS may be reduced when DMSO is used as a vehicle.…”

“…An organic extract of BDS has been previously shown to be a significant cytotoxic and genotoxic threat to human bronchial epithelial cells (Catallo et al 2001). However, the mechanisms of action of BDS have yet to be identified.…”

“…Previous reports have suggested that BDS is highly reactive and may produce reactive oxygen species (ROS) in cultured normal human bronchial epithelia (NHBE) cells (Catallo et al 2001). ROS can be produced in cells by either endogenous or exogenous processes and ROS have been shown to be involved in the development of cancer (Dreher and Junod 1996).…”