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Article

Carbon ions and X‑rays induce pro‑inflammatory effects in 3D oral mucosa models with and without PBMCs

  • Authors:
    • Viktoria Tschachojan
    • Henrike Schroer
    • Nicole Averbeck
    • Wolfgang Mueller-Klieser
  • View Affiliations / Copyright

    Affiliations: Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany, GSI Helmholtz Center for Heavy Ion Research, Darmstadt, Germany
  • Pages: 1820-1828
    |
    Published online on: August 22, 2014
       https://doi.org/10.3892/or.2014.3441
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Abstract

Oral mucositis is a severe complication of radiotherapy. Hence, it may constitute a serious medical safety risk for astronauts during extended space flights, such as missions to Mars, during which they are exposed to heavy-ion irradiation. For risk assessment of developing radiation-induced mucositis, a three-dimensional (3D) organotypic oral mucosa model was irradiated with 12C heavy ions or X‑rays. The present study focused mainly on early radiation‑induced effects, such as the activation of nuclear factor κB (NFκB) and the expression or release of pro-inflammatory marker molecules. The 3D oral mucosa models with or without peripheral blood mononuclear cells (PBMCs) were irradiated with X‑rays or 12C heavy ions followed by snap freezing. Subsequently, cryosections were derived from the specimens, which were immunostained for analysis of compactness, DNA double strand breaks (DSB) and activation of NFκB. Radiation‑induced release of interleukin 6 (IL6) and interleukin 8 (IL8) was quantified by ELISA. Quantification of the DNA damage in irradiated mucosa models revealed distinctly more DSB after heavy-ion irradiation compared to X‑rays at definite time points, suggesting a higher gene toxicity of heavy ions. NFκB activation was observed after treatment with X‑rays or 12C particles. ELISA analyses showed significantly higher IL6 and IL8 levels after irradiation with X‑rays and 12C particles compared to non-irradiated controls, whereas co‑cultures including PBMCs released 2 to 3-fold higher interleukin concentrations compared to mucosa models without PBMCs. In this study, we demonstrated that several pro-inflammatory markers are induced by X‑rays and heavy-ion irradiation within an oral mucosa model. This suggests that oral mucositis indeed poses a risk for astronauts on extended space flights.
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1 

Hall EJ and Giaccia A: Radiobiology for the Radiologist. 7th edition. Lippincott Williams & Wilkins; Philadelphia, PA: 2012

2 

Hawkey A: Physiological and biomechanical considerations for a human Mars mission. J Br Interplanet Soc. 58:117–130. 2005.PubMed/NCBI

3 

Cucinotta FA, Kim MHY and Chappell LJ: Evaluating shielding approaches to reduce space radiation cancer risks. NASA Center for AeroSpace Information; May. pp. 1–35. 2012

4 

Cucinotta FA, Kim MHY and Ren L: Evaluating shielding effectiveness for reducing space radiation cancer risks. Radiat Meas. 41:1173–1185. 2006. View Article : Google Scholar

5 

Durante M and Cucinotta FA: Heavy ion carcinogenesis and human space exploration. Nat Rev Cancer. 8:465–472. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Schulz-Ertner D, Haberer T, Scholz M, et al: Acute radiation-induced toxicity of heavy ion radiotherapy delivered with intensity modulated pencil beam scanning in patients with base of skull tumors. Radiother Oncol. 64:189–195. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Sonis ST and Fey EG: Oral complications of cancer therapy. Oncology. 16:680–686. 2002.PubMed/NCBI

8 

Vissink A, Jansma J, Spijkervet FK, Burlage FR and Coppes RP: Oral sequelae of head and neck radiotherapy. Crit Rev Oral Biol Med. 14:199–212. 2003. View Article : Google Scholar

9 

Jensen AD, Nikoghosyan AV, Ecker S, Ellerbrock M, Debus J and Münter MW: Carbon ion therapy for advanced sinonasal malignancies: feasibility and acute toxicity. Radiat Oncol. 6:302011. View Article : Google Scholar : PubMed/NCBI

10 

Fleckenstein J, Kühne M, Seegmüller K, et al: The impact of individual in vivo repair of DNA double-strand breaks on oral mucositis in adjuvant radiotherapy of head-and-neck cancer. Int J Radiat Oncol Biol Phys. 81:1465–1472. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Sonis ST: Oral mucositis in head and neck cancer: risk, biology, and management. Am Soc Clin Oncol Educ Book. 236–240. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Naidu MU, Ramana GV, Rani PU, Mohan IK, Suman A and Roy P: Chemotherapy-induced and/or radiation therapy-induced oral mucositis - complicating the treatment of cancer. Neoplasia. 6:423–431. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Hickok JT, Morrow GR, Roscoe JA, Mustian K and Okunieff P: Occurrence, severity, and longitudinal course of twelve common symptoms in 1129 consecutive patients during radiotherapy for cancer. J Pain Symptom Manage. 30:433–442. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Porta C, Larghi P, Rimoldi M, Totaro MG, Allavena P, Mantovani A and Sica A: Cellular and molecular pathways linking inflammation and cancer. Immunobiology. 214:761–777. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Karin M and Greten FR: NF-κB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 5:749–759. 2005.

16 

Karin M: NF-κB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol. 1:a0001412009.

17 

Magné N, Toillon RA, Bottero V, Didelot C, Houtte PV, Gérard JP and Peyron JF: NF-κB modulation and ionizing radiation: mechanisms and future directions for cancer treatment. Cancer Lett. 231:158–168. 2006.

18 

Boxman IL, Ruwhof C, Boerman OC, Löwik CW and Ponec M: Role of fibroblasts in the regulation of proinflammatory interleukin IL-1, IL-6 and IL-8 levels induced by keratinocyte-derived IL-1. Arch Dermatol Res. 288:391–398. 1996. View Article : Google Scholar : PubMed/NCBI

19 

Sawicki G, Marcoux Y, Sarkhosh K, Tredget E and Ghahary A: Interaction of keratinocytes and fibroblasts modulates the expression of matrix metalloproteinases-2 and -9 and their inhibitors. Mol Cell Biochem. 269:209–216. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Wang Z, Wang Y, Farhangfar F, Zimmer M and Zhang Y: Enhanced keratinocyte proliferation and migration in co-culture with fibroblasts. PLoS One. 7:e409512012. View Article : Google Scholar : PubMed/NCBI

21 

Werner S, Krieg T and Smola H: Keratinocyte-fibroblast interactions in wound healing. J Invest Dermatol. 127:998–1008. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Sonis ST: The pathobiology of mucositis. Nat Rev Cancer. 4:277–284. 2004. View Article : Google Scholar

23 

Bonan PRF, Kaminagakura E, Pires FR, Vargas PA and de Almeida OP: Cytokeratin expression in initial oral mucositis of head and neck irradiated patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 101:205–211. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Basu S, Rosenzweig KR, Youmell M and Price BD: The DNA-dependent protein kinase participates in the activation of NFκB following DNA damage. Biochem Biophys Res Commun. 247:79–83. 1998.

25 

Lee SJ, Dimtchev A, Lavin MF, Dritschilo A and Jung M: A novel ionizing radiation-induced signaling pathway that activates the transcription factor NF-κB. Oncogene. 17:1821–1826. 1998.PubMed/NCBI

26 

Piret B, Schoonbroodt S and Piette J: The ATM protein is required for sustained activation of NF-κB following DNA damage. Oncogene. 18:2261–2271. 1999.PubMed/NCBI

27 

Sonis ST: New thoughts on the initiation of mucositis. Oral Dis. 16:597–600. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Ben-Neriah Y and Karin M: Inflammation meets cancer, with NF-κB as the matchmaker. Nat Immunol. 12:715–723. 2011.

29 

Hellweg CE, Baumstark-Khan C, Schmitz C, et al: Carbon-ion-induced activation of the NF-κB pathway. Radiat Res. 175:424–431. 2011.PubMed/NCBI

30 

Colley HE, Eves PC, Pinnock A, Thornhill MH and Murdoch C: Tissue-engineered oral mucosa to study radiotherapy-induced oral mucositis. Int J Radiat Biol. 89:907–914. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Tobita T, Izumi K and Feinberg SE: Development of an in vitro model for radiation-induced effects on oral keratinocytes. Int J Oral Maxillofac Surg. 39:364–370. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Lambros MP, Parsa C, Mulamalla H, et al: Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis. Biochem Biophys Res Commun. 405:102–106. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Brat DJ, Bellail AC and Van Meir EG: The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro Oncol. 7:122–133. 2005. View Article : Google Scholar : PubMed/NCBI

34 

Xie K: Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev. 12:375–391. 2001. View Article : Google Scholar

35 

Yin Y, Si X, Gao Y, Gao L and Wang J: The nuclear factor-κB correlates with increased expression of interleukin-6 and promotes progression of gastric carcinoma. Oncol Rep. 29:34–38. 2013.

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Copy and paste a formatted citation
Spandidos Publications style
Tschachojan V, Schroer H, Averbeck N and Mueller-Klieser W: Carbon ions and X‑rays induce pro‑inflammatory effects in 3D oral mucosa models with and without PBMCs. Oncol Rep 32: 1820-1828, 2014.
APA
Tschachojan, V., Schroer, H., Averbeck, N., & Mueller-Klieser, W. (2014). Carbon ions and X‑rays induce pro‑inflammatory effects in 3D oral mucosa models with and without PBMCs. Oncology Reports, 32, 1820-1828. https://doi.org/10.3892/or.2014.3441
MLA
Tschachojan, V., Schroer, H., Averbeck, N., Mueller-Klieser, W."Carbon ions and X‑rays induce pro‑inflammatory effects in 3D oral mucosa models with and without PBMCs". Oncology Reports 32.5 (2014): 1820-1828.
Chicago
Tschachojan, V., Schroer, H., Averbeck, N., Mueller-Klieser, W."Carbon ions and X‑rays induce pro‑inflammatory effects in 3D oral mucosa models with and without PBMCs". Oncology Reports 32, no. 5 (2014): 1820-1828. https://doi.org/10.3892/or.2014.3441
Copy and paste a formatted citation
x
Spandidos Publications style
Tschachojan V, Schroer H, Averbeck N and Mueller-Klieser W: Carbon ions and X‑rays induce pro‑inflammatory effects in 3D oral mucosa models with and without PBMCs. Oncol Rep 32: 1820-1828, 2014.
APA
Tschachojan, V., Schroer, H., Averbeck, N., & Mueller-Klieser, W. (2014). Carbon ions and X‑rays induce pro‑inflammatory effects in 3D oral mucosa models with and without PBMCs. Oncology Reports, 32, 1820-1828. https://doi.org/10.3892/or.2014.3441
MLA
Tschachojan, V., Schroer, H., Averbeck, N., Mueller-Klieser, W."Carbon ions and X‑rays induce pro‑inflammatory effects in 3D oral mucosa models with and without PBMCs". Oncology Reports 32.5 (2014): 1820-1828.
Chicago
Tschachojan, V., Schroer, H., Averbeck, N., Mueller-Klieser, W."Carbon ions and X‑rays induce pro‑inflammatory effects in 3D oral mucosa models with and without PBMCs". Oncology Reports 32, no. 5 (2014): 1820-1828. https://doi.org/10.3892/or.2014.3441
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