Skip to main content
SpringerLink
Log in

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

  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

1,3-Butadiene, an important petrochemical, is commonly burned off when excess amounts need to be destroyed. This combustion process produces butadiene soot (BDS), which is composed of a complex mixture of polycyclic aromatic hydrocarbons in particulates ranging in size from <1 μm to 1 mm. An organic extract of BDS is both cytotoxic and genotoxic to normal human bronchial epithelial (NHBE) cells. Based on the oxidizing potential of BDS, we hypothesized that an organic extract of this particulate matter would (1) cause enzyme inactivation due to protein amino acid oxidation and (2) induce oxidative DNA damage in NHBE cells. Thus, our aims were to determine the effect of butadiene soot ethanol extract (BSEE) on both enzyme activity and the expression of proteins involved in the repair of oxidative DNA damage. Catalase was found to be sensitive to BDS as catalase activity was potently diminished in the presence of BSEE. Using Western analysis, both the alpha isoform of human 8-oxoguanine DNA glycosylase (α-hOGG1) and human apurinic/apyrimidinic endonuclease (APE-1) were shown to be significantly overexpressed as compared to untreated controls after exposure of NHBE cells to BSEE. Our results indicate that BSEE is capable of effectively inactivating the antioxidant enzyme catalase, presumably via oxidation of protein amino acids. The presence of oxidized biomolecules may partially explain the extranuclear fluorescence that is detected when NHBE cells are treated with an organic extract of BDS. Overexpression of both α-hOGG1 and APE-1 proteins following treatment of NHBE cells with BSEE suggests that this mixture causes oxidative DNA damage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

APE-1:

Apurinic/apyrimidinic endonuclease

BDS:

Butadiene soot

BEAS-2B cells:

Immortalized nontumorigenic human bronchial epithelial cells

BEGM:

Bronchial epithelial growth medium

BSDE:

Butadiene soot DMSO extract

BSEE:

Butadiene soot ethanol extract

DMSO:

Dimethyl sulfoxide

EtOH:

Ethanol

HBE cells:

Human bronchial epithelial cells

hMTH1:

Human mutT homologue

hMYH:

Human mutY homolog

hOGG1:

Human 8-oxoguanine DNA glycosylase

NHBE cells:

Normal human bronchial epithelial cells

8-oxo-dG:

8-oxo-2′-deoxyguanosine

8-oxo-dGTP:

8-oxo-2′-deoxyguanosine triphosphate

PAHs:

Polycyclic aromatic hydrocarbons

ROS:

Reactive oxygen species

References

  • Aburatani H, Hippo Y, Ishida T, Takashima R, Matsuba C, Kodama T, et al. Cloning and characterization of mammalian 8-hydroxyguanine-specific DNA glycosylase/apurinic, apyrimidinic lyase, a functional mutM homologue. Cancer Res. 1997;57:2151–6.

    PubMed  CAS  Google Scholar 

  • Albrecht C, Knaapen AM, Becker A, Hohr D, Haberzettl P, van Schooten FJ, et al. The crucial role of particle surface reactivity in respirable quartz-induced reactive oxygen/nitrogen species formation and APE/Ref-1 induction in rat lung. Respir Res. 2005;2:129. doi:10.1186/1465-9921-6-129.

    Article  CAS  Google Scholar 

  • Brunnemann KD, Kagan MR, Cox JE, Hoffmann D. Determination of benzene, toluene and 1,3-butadiene in cigarette smoke by GC–MDS. Exp Pathol. 1989;37:108–13.

    PubMed  CAS  Google Scholar 

  • Catallo WJ. Polycyclic aromatic hydrocarbons in combustion residues from 1,3-butadiene. Chemosphere 1998;37:143–57. doi:10.1016/S0045-6535(98)00030-7.

    Article  CAS  Google Scholar 

  • Catallo WJ, Kennedy CH, Henk W, Barker SA, Grace SC, Penn A. Combustion products of 1,3-butadiene are cytotoxic and genotoxic to human bronchial epithelial cells. Environ Health Perspect. 2001;109:965–71. doi:10.2307/3455000.

    Article  PubMed  CAS  Google Scholar 

  • Cerutti PA. Oxy-radicals and cancer. Lancet 1994;344:862–3. doi:10.1016/S0140-6736(94)92832-0.

    Article  PubMed  CAS  Google Scholar 

  • Cheng KC, Cahill DS, Kasai H, Nishimura S, Loeb LA. 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G→T and A→C substitutions. J Biol Chem. 1992;267:166–72.

    PubMed  CAS  Google Scholar 

  • Cohen G, Kim M, Ogwu V. A modified catalase assay suitable for a plate reader and for the analysis of brain cell cultures. J Neurosci Methods. 1996;67:53–6. doi:10.1016/0165-0270(96)00011-8.

    Article  PubMed  CAS  Google Scholar 

  • Demple B, Herman T, Chen DS. Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes. Proc Natl Acad Sci USA. 1991;88:11450–4. doi:10.1073/pnas.88.24.11450.

    Article  PubMed  CAS  Google Scholar 

  • Dreher D, Junod AF. Role of oxygen free radicals in cancer development. Eur J Cancer. 1996;32A:30–8. doi:10.1016/0959-8049(95)00531-5.

    Article  PubMed  CAS  Google Scholar 

  • Evans AR, Limp-Foster M, Kelley MR. Going APE over ref-1. Mutat Res. 2000;461:83–108.

    PubMed  CAS  Google Scholar 

  • Grune T, Reinheckel T, Joshi M, Davies KJA. Protein degradation in cultured liver epithelial cells during oxidative stress. J Biol Chem. 1995;270:2344–51. doi:10.1074/jbc.270.5.2344.

    Article  PubMed  CAS  Google Scholar 

  • Grune T, Reinheckel T, Davies KJA. Degradation of oxidized proteins in mammalian cells. FASEB J. 1997;11:526–34.

    PubMed  CAS  Google Scholar 

  • Halliwell B, Aruoma OI. DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems. FEBS Lett. 1991;28:9–19. doi:10.1016/0014-5793(91)80347-6.

    Article  Google Scholar 

  • Hashiguchi K, Stuart JA, de Souza-Pinto NC, Bohr VA. The C-terminal αO helix of human Ogg1 is essential for 8-oxoguanine DNA glycosylase activity: the mitochondrial β-Ogg1 lacks this domain and does not have glycosylase activity. Nucleic Acids Res. 2004;32:5596–608. doi:10.1093/nar/gkh863.

    Article  PubMed  CAS  Google Scholar 

  • He YH 2nd, Wu M, Kobune M, Xu Y, Kelley MR, Martin WJ. Expression of yeast apurinic/apyrimidinic endonuclease (APN1) protects lung epithelial cells from bleomycin toxicity. Am J Respir Cell Mol Biol. 2001;25:692–8.

    PubMed  CAS  Google Scholar 

  • Hibi K, Liu Q, Beaudry GA, Madden SL, Westra WH, Wehage SL, et al. Serial analysis of gene expression in non-small cell lung cancer. Cancer Res. 1998;58:5690–4.

    PubMed  CAS  Google Scholar 

  • Iida T, Furuta A, Kawashima M, Nishida J, Nakabeppu Y, Iwaki T. Accumulation of 8-oxo-2′-deoxyguanosine and increased expression of hMTH1 protein in brain tumors. Neuro-oncol 2001;3:73–81. doi:10.1215/15228517-3-2-73.

    Article  PubMed  CAS  Google Scholar 

  • Kennedy CH, Cueto R, Belinsky SA, Lechner JF, Pryor WA. Overexpression of hMTH1 mRNA: a molecular marker of oxidative stress in lung cancer cells. FEBS Lett. 1998;429:17–20. doi:10.1016/S0014-5793(98)00505-5.

    Article  PubMed  CAS  Google Scholar 

  • Kennedy CH, Pass HI, Mitchell JB. Expression of human MutT homologue (hMTH1) protein in primary non-small-cell lung carcinomas and histologically normal surrounding tissue. Free Radic Biol Med. 2003;34:1447–57. doi:10.1016/S0891-5849(03)00176-X.

    Article  PubMed  CAS  Google Scholar 

  • Kim HN, Morimoto Y, Tsuda T, Ootsuyama Y, Hirohashi M, Hirano T, et al. Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos. Carcinogenesis 2001;22:265–9. doi:10.1093/carcin/22.2.265.

    Article  PubMed  CAS  Google Scholar 

  • Kremer TM, Rinne ML, Xu Y, Chen XM, Kelley MR. Protection of pulmonary epithelial cells from oxidative stress by hMYH adenine glycosylase. Respir Res 2004;5:16. doi:10.1186/1465-9921-5-16.

    Article  PubMed  CAS  Google Scholar 

  • Kuchino Y, Mori F, Kasai H, Inoue H, Iwai S, Miura K, et al. Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues. Nature 1987;327:77–9. doi:10.1038/327077a0.

    Article  PubMed  CAS  Google Scholar 

  • Maki H, Sekiguchi M. MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis. Nature 1992;355:273–5. doi:10.1038/355273a0.

    Article  PubMed  CAS  Google Scholar 

  • Mambo E, Chatterjee A, de Souza-Pinto NC, Mayard S, Hogue BA, Hoque MO, et al. Oxidized guanine lesions and hOgg1 activity in lung cancer. Oncogene 2005;24:4496–508. doi:10.1038/sj.onc.1208669.

    Article  PubMed  CAS  Google Scholar 

  • Mo JY, Maki H, Sekiguchi M. Hydrolytic elimination of a mutagenic nucleotide, 8-oxodGTP, by human 18-kilodalton protein: sanitization of nucleotide pool. Proc Natl Acad Sci USA. 1992;89:11021–5. doi:10.1073/pnas.89.22.11021.

    Article  PubMed  CAS  Google Scholar 

  • Mori Y, Murakami S, Sagae T, Hayashi H, Sakata M, Sagai M, et al. Inhibition of catalase activity in vitro by diesel exhaust particles. J Toxicol Environ Health. 1996;47:125–34. doi:10.1080/009841096161834.

    Article  PubMed  CAS  Google Scholar 

  • Murphy G Jr, Rouse RL, Polk WW, Henk WG, Barker SA, Boudreaux J, et al. Combustion-derived hydrocarbons localize to lipid droplets in respiratory cells. Am J Respir Cell Mol Biol. 2007. doi:10.1165/rcmb.2007-0204OC.

  • Nishioka K, Ohtsubo T, Oda H, Fujiwara T, Kang D, Sugimachi K, et al. Expression and differential intracellular localization of two major forms of human 8-oxoguanine DNA glycosylase encoded by alternatively spliced OGG1 mRNAs. Mol Biol Cell. 1999;10:1637–52.

    PubMed  CAS  Google Scholar 

  • Okamoto K, Toyokuni S, Kim WJ, Ogawa O, Kakehi Y, Arao S, et al. Overexpression of human mutT homologue gene messenger RNA in renal-cell carcinoma: evidence of persistent oxidative stress in cancer. Int J Cancer. 1996;65:437–41. doi:10.1002/(SICI)1097-0215(19960208)65:4<437::AID-IJC7>3.0.CO;2-Y.

    Article  PubMed  CAS  Google Scholar 

  • Paz-Elizur T, Krupsky M, Elinger D, Schechtman E, Livneh Z. Repair of the oxidative DNA damage 8-oxoguanine as a biomarker for lung cancer risk. Cancer Biomark. 2005;1:201–5.

    PubMed  CAS  Google Scholar 

  • Penn A, Murphy G, Barker S, Henk W, Penn L. Combustion-derived ultrafine particles transport organic toxicants to target respiratory cells. Environ Health Perspect. 2005;113:956–63.

    Article  PubMed  CAS  Google Scholar 

  • Puglisi F, Aprile G, Minisini AM, Barbone F, Cataldi P, Tell G, et al. Prognostic significance of Ape1/ref-1 subcellular localization in non-small cell lung carcinomas. Anticancer Res. 2001;21:4041–9.

    PubMed  CAS  Google Scholar 

  • Reddel RR, Ke Y, Gerwin BI, McMenamin MG, Lechner JF, Su RT, et al. Transformation of human bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 hybrid virus, or transfection via strontium phosphate coprecipitation with a plasmid containing SV40 early region genes. Cancer Res. 1988;48:1904–9.

    PubMed  CAS  Google Scholar 

  • Reddel RR, Salghetti SE, Willey JC, Ohnuki Y, Ke Y, Gerwin BI, et al. Development of tumorigenicity in simian virus 40-immortalized human bronchial epithelial cell lines. Cancer Res. 1993;53:985–91.

    PubMed  CAS  Google Scholar 

  • Rouse RL, Murphy G, Boudreux MJ, Paulsen DB, Penn AL. Soot nanoparticles promote biotransformation, oxidative stress, and inflammation in murine lungs. Am J Respir Cell Mol Biol. 2008. doi:10.1165/rcmb.2008-0057OC.

  • Shibutani S, Takeshita M, Grollman AP. Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG. Nature 1991;349:431–4. doi:10.1038/349431a0.

    Article  PubMed  CAS  Google Scholar 

  • Shinmura K, Yamaguchi S, Saitoh T, Takeuchi-Sasaki M, Kim SR, Nohmi T, et al. Adenine excisional repair function of MYH protein on the adenine:8-hydroxyguanine base pair in double-stranded DNA. Nucleic Acids Res. 2000;28:4912–8. doi:10.1093/nar/28.24.4912.

    Article  PubMed  CAS  Google Scholar 

  • Takao M, Aburatani H, Kobayashi K, Yasui A. Mitochondrial targeting of human DNA glycosylases for repair of oxidative DNA damage. Nucleic Acids Res. 1998;26:2917–22. doi:10.1093/nar/26.12.2917.

    Article  PubMed  CAS  Google Scholar 

  • Toyokuni S, Mori T, Dizdaroglu M. DNA base modifications in renal chromatin of Wistar rats treated with a renal carcinogen, ferric nitrilotriacetate. Int J Cancer 1994;57:123–8. doi:10.1002/ijc.2910570122.

    Article  PubMed  CAS  Google Scholar 

  • Toyokuni S, Okamoto K, Yodoi J, Hiai H. Persistent oxidative stress in cancer. FEBS Lett. 1995;358:1–3. doi:10.1016/0014-5793(94)01368-B.

    Article  PubMed  CAS  Google Scholar 

  • Tsurudome Y, Hirano T, Yamato H, Tanaka I, Sagai M, Hirano H, et al. Changes in levels of 8-hydroxyguanine in DNA, its repair and OGG1 mRNA in rat lungs after intratracheal administration of diesel exhaust particles. Carcinogenesis. 1999;20:1573–6. doi:10.1093/carcin/20.8.1573.

    Article  PubMed  CAS  Google Scholar 

  • Wani G, Milo GE, D’Ambrosio SM. Enhanced expression of the 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase gene in human breast tumor cells. Cancer Lett. 1998;125:123–30. doi:10.1016/S0304-3835(97)00507-7.

    Article  PubMed  CAS  Google Scholar 

  • Wikman H, Risch A, Klimek F, Schmezer P, Spigelhalder B, Dienemann H, et al. hOGG1 polymorphism and loss of heterozygosity (LOH): significance for lung cancer susceptibility in a caucasian population. Int J Cancer 2000;15:932–7. doi:10.1002/1097-0215(20001215)88:6<932::AID-IJC15>3.0.CO;2-P.

    Article  Google Scholar 

  • Yang S, Irani K, Heffron SE, Jurnak F, Meyskens FL Jr. Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1) in human melanoma and identification of the therapeutic potential of resveratrol as an APE/Ref-1 inhibitor. Mol Cancer Ther. 2005;4:1923–35. doi:10.1158/1535-7163.MCT-05-0229.

    Article  PubMed  CAS  Google Scholar 

  • Zhou H, Cheng B, Lin J. Expression of DNA repair enzyme hMTH1 mRNA and protein in hepatocellular carcinoma. J Huazhong Univ Sci Technolog Med Sci. 2005;25:389–92.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Blvd., Erie, PA, 16509-1025, USA

    Christopher H. Kennedy

  2. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA

    W. James Catallo

  3. School of the Coast and Environment, Louisiana State University, Baton Rouge, LA, USA

    Vincent L. Wilson

  4. Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    James B. Mitchell

Authors
  1. Christopher H. Kennedy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. James Catallo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vincent L. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James B. Mitchell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christopher H. Kennedy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kennedy, C.H., Catallo, W.J., Wilson, V.L. et al. Combustion products of 1,3-butadiene inhibit catalase activity and induce expression of oxidative DNA damage repair enzymes in human bronchial epithelial cells. Cell Biol Toxicol 25, 457–470 (2009). https://doi.org/10.1007/s10565-008-9100-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-008-9100-z

Keywords

Search

Navigation