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Can proteomics predict the prognosis in chronic dioxin intoxication?

  • Daniela PelclovaEmail author
  • Pavel Talacko
  • Tomas Navratil
  • Blanka Zamostna
  • Zdenka Fenclova
  • Stepanka Vlckova
  • Sergey Zakharov
Original Paper
  • 9 Downloads

Abstract

Untargeted proteomic analysis of exhaled breath condensate (EBC) was used to estimate the effects and prognosis of chronic intoxication with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to elucidate the mechanisms involved. EBC was collected from eight males (72.4 ± 1.3 years) exposed to TCDD in 1965–1968 and seven control males (66 ± 16 years). The median TCDD blood level was 112 (46–390) ng/kg fat in the patients 50 years after exposure and 12 ng/kg in the controls. The shotgun method for identifying proteins was performed after proteolytic digestion and high-performance liquid chromatography combined with mass spectrometry. Raw data were evaluated using the MaxQuant software and protein atlas. A total of 332 proteins were detected: one protein was unique to TCDD patients and 11 to the controls. These proteins may have come from many organs, in addition to the lungs and bronchi. The salivary contribution based on alpha amylase proportion to the overall protein’s intensity was only 0.003%. The intensity of nine proteins was correlated with TCDD plasma level (two positively, seven negatively), but not with alpha amylase. This excludes saliva contamination, as this enzyme is the marker of salivary contamination. Several of the changes in intensity were associated with an unfavourable prognosis of cancers. Proteomics of EBC may bring new information and point to the mechanisms by which this highly toxic chemical and human carcinogen potentially affects any organ.

Graphic abstract

Keywords

Exhaled breath condensate TCDD Cancers Proteins 

Notes

Acknowledgements

Projects PROGRES Q25/LF1 and Q29/LF1.

References

  1. 1.
    Cerna M, Kratenova J, Zejglicova K, Brabec M, Maly M, Smid J, Crhova S, Grabic R, Volf J (2007) Chemosphere 67:S238CrossRefGoogle Scholar
  2. 2.
    Trnovec T, Jusko TA, Sovcikova E, Lancz K, Chovancova J, Patayova H, Palkovicova L, Drobna B, Langer P, Van den Berg M, Dedik L, Wimmerova S (2013) Environ Health Perspect 121:886CrossRefGoogle Scholar
  3. 3.
    Loomis D, Guha N, Hall AL, Straif K (2018) Occup Environ Med 75:593CrossRefGoogle Scholar
  4. 4.
    Dziubanek G, Marchwińska E, Hajok I, Piekut A (2016) Cent Eur J Public Health 24:115CrossRefGoogle Scholar
  5. 5.
    Sorg O (2014) Toxicol Lett 230:225CrossRefGoogle Scholar
  6. 6.
    Saurat JH, Sorg O (2010) Dermatology 221:23CrossRefGoogle Scholar
  7. 7.
    Pelclova D, Fenclova Z, Dlaskova Z, Urban P, Lukas E, Prochazka B, Rappe C, Preiss J, Kocan A, Vejlupkova J (2001) Arch Environ Health 56:493CrossRefGoogle Scholar
  8. 8.
    Pelclova D, Fenclova Z, Preiss J, Prochazka B, Spacil J, Dubska Z, Okrouhlik B, Lukas E, Urban P (2002) Int Arch Occup Environ Health 75(Suppl):S60Google Scholar
  9. 9.
    Pelclova D, Prazny M, Skrha J, Fenclova Z, Kalousova M, Urban P, Navratil T, Senholdova Z, Smerhovsky Z (2007) Hum Exp Toxicol 26:705CrossRefGoogle Scholar
  10. 10.
    Urban P, Pelclova D, Lukas E, Kupka K, Preiss J, Fenclova Z, Smerhovsky Z (2007) Eur J Neurol 14:213CrossRefGoogle Scholar
  11. 11.
    Jeanneret F, Boccard J, Badoud F, Sorg O, Tonoli D, Pelclova D, Vlckova S, Rutledge DN, Samer CF, Hochstrasser D, Saurat JH, Rudaz S (2014) Toxicol Lett 230:234CrossRefGoogle Scholar
  12. 12.
    Pelclova D, Navratil T, Fenclova Z, Vlckova S, Kupka K, Urban P, Ridzon P, Zikan V, Landova L, Syslova K, Kuzma M, Kacer P (2011) Neuro Endocrinol Lett 32:71Google Scholar
  13. 13.
    Pelclova D, Navratil T, Vlckova S, Fenclova Z, Pelcl T, Kacerova T, Kacer P (2018) Monatsh Chem 149:1579CrossRefGoogle Scholar
  14. 14.
    Pelclova D, Urban P, Fenclova Z, Vlckova S, Ridzon P, Kupka K, Meckova Z, Bezdicek O, Navratil T, Rosmus J, Zakharov S (2018) Basic Clin Pharmacol Toxicol 122:271CrossRefGoogle Scholar
  15. 15.
    Pelcl T, Skrha J, Prazny M, Vlckova S, Fenclova Z, Navratil T, Malik J, Diblik P, Zikan V, Pelclova D (2018) Basic Clin Pharmacol Toxicol 123:356CrossRefGoogle Scholar
  16. 16.
    Cox J, Hein MY, Luber CA, Paron I, Nagaraj N, Mann M (2014) Mol Cell Proteom 13:2513CrossRefGoogle Scholar
  17. 17.
    Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto C, Odeberg J, Djureinovic D, Takanen J, Hober S, Alm T, Edqvist PH, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk J, Hamsten M, Forsberg M, Persson L, Johansson F, Zwahlen M, Nielsen J, Ponten F (2018) The human protein atlas. https://www.proteinatlas.org/. Accessed 18 Nov 2018
  18. 18.
    Yu GC, Wang LG, Han YY, He QY (2012) OMICS 16:284CrossRefGoogle Scholar
  19. 19.
    Hayes SA, Haefliger S, Harris B, Pavlakis N, Clarke SJ, Molloy MP, Howell VM (2016) J Breath Res 10:034001CrossRefGoogle Scholar
  20. 20.
    Pelclova D, Zdimal V, Kacer P, Fenclova Z, Vlckova S, Syslova K, Navratil T, Schwarz J, Zikova N, Barosova H, Turci F, Komarc M, Pelcl T, Belacek J, Kukutschova J, Zakharov S (2016) J Breath Res 10:016004CrossRefGoogle Scholar
  21. 21.
    Pelclova D, Zdimal V, Kacer P, Zikova N, Komarc M, Fenclova Z, Vlckova S, Schwarz J, Makes O, Syslova K, Navratil T, Turci F, Corazzari I, Zakharov S, Bello D (2017) Nanotoxicology 11:52CrossRefGoogle Scholar
  22. 22.
    Muccilli V, Saletti R, Cunsolo V, Ho J, Gili E, Conte E, Sichili S, Vancheri C, Foti S (2015) J Pharm Biomed Anal 105:134CrossRefGoogle Scholar
  23. 23.
    Gorlin JB, Yamin R, Egan S, Stewart M, Stossel TP, Kwiatkowski DJ, Hartwig JH (1990) J Cell Biol 111:1089CrossRefGoogle Scholar
  24. 24.
    Roy MG, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, Tuvim MJ, Adachi R, Romo I, Bordt AS, Bowden MG, Sisson JH, Woodruff PG, Thornton DJ, Rousseau K, De la Garza MM, Moghaddam SJ, Karmouty-Quintana H, Blackburn MR, Drouin SM, Davis CW, Terrell KA, Grubb BR, O’Neal WK, Flores SC, Cota-Gomez A, Lozupone CA, Donnelly JM, Watson AM, Hennessy CE, Keith RC, Yang IV, Barthel L, Henson PM, Janssen WJ, Schwartz DA, Boucher RC, Dickey BF, Evans CM (2014) Nature 505:412CrossRefGoogle Scholar
  25. 25.
    Lacombe M, Marie-Desvergne C, Combes F, Kraut A, Bruley C, Vandenbrouck Y, Mossuz VC, Coute Y, Brun V (2018) J Breath Res 12:021001CrossRefGoogle Scholar
  26. 26.
    Butler MW, Fukui T, Salit J, Shaykhiev R, Mezey JG, Hackett NR, Crystal RG (2011) Cancer Res 71:2572CrossRefGoogle Scholar
  27. 27.
    Sulkava M, Raitoharju E, Levula M, Seppala I, Lyytikainen LP, Mennander A, Jarvinen O, Zeitlin R, Salenius JP, Illig T, Klopp N, Mononen N, Laaksonen R, Kahonen M, Oksala N, Lehtimaki T (2017) Sci Rep 7:41483CrossRefGoogle Scholar
  28. 28.
    Perez P, Adriaansen J, Goldsmith CM, Zheng C, Baum BJ (2011) Oral Dis 17:476CrossRefGoogle Scholar
  29. 29.
    Kurova VS, Anaev EC, Kononikhin AS, Fedorchenko KY, Popov IA, Kalupov TL, Bratanov DO, Nikolaev EN, Varfolomeev SD (2009) Clin Chem Lab Med 47:706CrossRefGoogle Scholar
  30. 30.
    Hu Q, Rice RH, Qin Q, Phinney BS, Eigenheer RA, Bao WJ, Zhao B (2013) J Proteome Res 12:5340CrossRefGoogle Scholar
  31. 31.
    Masuda T, Tomita M, Ishihama Y (2008) J Proteome Res 7:731CrossRefGoogle Scholar
  32. 32.
    Phark S, Park SY, Chang YS, Choi S, Lim JY, Kim Y, Seo JB, Jung WW, Sul D (2016) Biochim Biophys Acta Proteins Proteom 1864:584CrossRefGoogle Scholar
  33. 33.
    Hebert AS, Richards AL, Bailey DJ, Ulbrich A, Coughlin EE, Westphall MS, Coon JJ (2014) Mol Cell Proteom 13:339CrossRefGoogle Scholar
  34. 34.
    Uniprot (2018) Database UniProtKB. https://www.uniprot.org/uniprot/. Accessed 18 Nov 2018
  35. 35.
    Tyanova S, Temu T, Sinitcyn P, Carlson A, Hein MY, Geiger T, Mann M, Cox J (2016) Nat Methods 13:731CrossRefGoogle Scholar
  36. 36.
    Lopez-Sanchez LM, Jurado-Gamez B, Feu-Collado N, Valverde A, Canas A, Fernandez-Rueda JL, Aranda E, Rodriguez-Ariza A (2017) Am J Physiol Lung Cell Mol Physiol 313:L664CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Occupational Medicine, First Faculty of MedicineCharles University and General University Hospital in PraguePragueCzech Republic
  2. 2.Laboratory of Mass Spectrometry BIOCEV, Faculty of ScienceCharles UniversityVestecCzech Republic
  3. 3.J. Heyrovský Institute of Physical Chemistry of the Czech Academy of SciencesPragueCzech Republic
  4. 4.Faculty of ScienceCharles University in PraguePragueCzech Republic

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