Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2001 Sep;109(9):965–971. doi: 10.1289/ehp.01109965

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

W J Catallo 1, C H Kennedy 1, W Henk 1, S A Barker 1, S C Grace 1, A Penn 1
PMCID: PMC1240449  PMID: 11673128

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.

Full Text

The Full Text of this article is available as a PDF (116.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames B. N., Shigenaga M. K., Hagen T. M. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915–7922. doi: 10.1073/pnas.90.17.7915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andersson H., Baechi T., Hoechl M., Richter C. Autofluorescence of living cells. J Microsc. 1998 Jul;191(Pt 1):1–7. doi: 10.1046/j.1365-2818.1998.00347.x. [DOI] [PubMed] [Google Scholar]
  3. Bayram H., Devalia J. L., Sapsford R. J., Ohtoshi T., Miyabara Y., Sagai M., Davies R. J. The effect of diesel exhaust particles on cell function and release of inflammatory mediators from human bronchial epithelial cells in vitro. Am J Respir Cell Mol Biol. 1998 Mar;18(3):441–448. doi: 10.1165/ajrcmb.18.3.2882. [DOI] [PubMed] [Google Scholar]
  4. Boland S., Baeza-Squiban A., Fournier T., Houcine O., Gendron M. C., Chévrier M., Jouvenot G., Coste A., Aubier M., Marano F. Diesel exhaust particles are taken up by human airway epithelial cells in vitro and alter cytokine production. Am J Physiol. 1999 Apr;276(4 Pt 1):L604–L613. doi: 10.1152/ajplung.1999.276.4.L604. [DOI] [PubMed] [Google Scholar]
  5. Carter J. D., Ghio A. J., Samet J. M., Devlin R. B. Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal-dependent. Toxicol Appl Pharmacol. 1997 Oct;146(2):180–188. doi: 10.1006/taap.1997.8254. [DOI] [PubMed] [Google Scholar]
  6. Fukasawa K., Vande Woude G. F. Mos overexpression in Swiss 3T3 cells induces meiotic-like alterations of the mitotic spindle. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3430–3434. doi: 10.1073/pnas.92.8.3430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hashimoto S., Gon Y., Takeshita I., Matsumoto K., Jibiki I., Takizawa H., Kudoh S., Horie T. Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation. Am J Respir Crit Care Med. 2000 Jan;161(1):280–285. doi: 10.1164/ajrccm.161.1.9904110. [DOI] [PubMed] [Google Scholar]
  8. Kennedy C. H., Mitchell C. E., Fukushima N. H., Neft R. E., Lechner J. F. Induction of genomic instability in normal human bronchial epithelial cells by 238Pu alpha-particles. Carcinogenesis. 1996 Aug;17(8):1671–1676. doi: 10.1093/carcin/17.8.1671. [DOI] [PubMed] [Google Scholar]
  9. Kodavanti U. P., Costa D. L., Bromberg P. A. Rodent models of cardiopulmonary disease: their potential applicability in studies of air pollutant susceptibility. Environ Health Perspect. 1998 Feb;106 (Suppl 1):111–130. doi: 10.1289/ehp.98106s1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Majno G., Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol. 1995 Jan;146(1):3–15. [PMC free article] [PubMed] [Google Scholar]
  11. Pellicer J. A., Pertusa J., Alcober V. Binucleate cells in the Ehrlich ascites tumor. Action of 5-fluorouracil. Biol Cell. 1987;60(3):255–257. doi: 10.1111/j.1768-322x.1987.tb00561.x. [DOI] [PubMed] [Google Scholar]
  12. Pou S., Ramos C. L., Gladwell T., Renks E., Centra M., Young D., Cohen M. S., Rosen G. M. A kinetic approach to the selection of a sensitive spin trapping system for the detection of hydroxyl radical. Anal Biochem. 1994 Feb 15;217(1):76–83. doi: 10.1006/abio.1994.1085. [DOI] [PubMed] [Google Scholar]
  13. Quay J. L., Reed W., Samet J., Devlin R. B. Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-kappaB activation. Am J Respir Cell Mol Biol. 1998 Jul;19(1):98–106. doi: 10.1165/ajrcmb.19.1.3132. [DOI] [PubMed] [Google Scholar]
  14. Rodilla V., Pellicer J. A., Pertusa J., Mothersill C. Induction of micronucleated and binucleate cells in Chinese hamster ovary (CHO) cells by cis-diamminedichloroplatinum (II): a morphological and morphometric study. Mutat Res. 1990 Jun;241(2):115–124. doi: 10.1016/0165-1218(90)90114-h. [DOI] [PubMed] [Google Scholar]
  15. Ronot X., Hecquet C., Larno S., Hainque B., Adolphe M. G2 arrest, binucleation, and single-parameter DNA flow cytometric analysis. Cytometry. 1986 May;7(3):286–290. doi: 10.1002/cyto.990070310. [DOI] [PubMed] [Google Scholar]
  16. Roque A. L., Pickren J. W. Enzymatic changes in fluorescent alveolar macrophages of the lungs of cigarette smokers. Acta Cytol. 1968 Nov-Dec;12(6):420–429. [PubMed] [Google Scholar]
  17. Siegfried J. M., Nesnow S. Cytotoxicity of chemical carcinogens towards human bronchial epithelial cells evaluated in a clonal assay. Carcinogenesis. 1984 Oct;5(10):1317–1322. doi: 10.1093/carcin/5.10.1317. [DOI] [PubMed] [Google Scholar]
  18. Siegfried J. M., Rudo K., Bryant B. J., Ellis S., Mass M. J., Nesnow S. Metabolism of benzo(a)pyrene in monolayer cultures of human bronchial epithelial cells from a series of donors. Cancer Res. 1986 Sep;46(9):4368–4371. [PubMed] [Google Scholar]
  19. Waterman D, Horsfield B, Leistner F, Hall K, Smith S. Quantification of polycyclic aromatic hydrocarbons in the NIST standard reference material (SRM1649A) urban dust using thermal desorption GC/MS. Anal Chem. 2000 Aug 1;72(15):3563–3567. doi: 10.1021/ac991372x. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES