Cooling of the oral mucosa to prevent adverse effects of chemotherapeutic agents: An in vitro study

Java Walladbegi, Sarah A Smith, Amy K Grayson, Craig Murdoch, Mats Jontell, Helen E Colley

Research output: Contribution to journalArticle (Academic Journal)peer-review

19 Citations (Scopus)


BACKGROUND: The cytotoxic effect of chemotherapeutic agents to the oral mucosa, as a side effect of cancer treatment, is a major problem. Cooling the oral mucosa using ice chips in conjunction with chemotherapy is known to reduce the severity of oral mucositis. However, although the use of ice chips is of clinical value, this method of cooling has inherent problems including discomfort for the patient, non-uniformity and fluctuations in cooling temperature throughout the oral cavity. Furthermore, despite being used clinically, it is not known what reduction in temperature is required to prevent oral mucositis. The aim of this study was therefore to determine in vitro if the cytotoxic effect of 5-fluorouracil (5-FU) on the oral mucosa could be reduced by lowering the temperature during chemotherapeutic treatment.

METHODS: Tissue-engineered oral mucosal (TEOM) models were incubated at 20, 25, 30 or 35°C for 30 minutes followed by exposure to a clinically relevant concentration of 5-FU (162 μg/mL) for 2 hours and compared with untreated models (35°C). Cell viability and inflammatory cytokine production (IL-6 and TNF-α) were measured using PrestoBlue® and ELISA, respectively.

RESULTS: TEOM models incubated at 20°C showed an increased cell viability and had a reduced IL-6 and TNF-α production compared to models treated with 5-FU incubated at 35°C.

CONCLUSION: This study demonstrates a reduced cytotoxic effect to the TEOM by reducing the temperature of the tissue during chemotherapy treatment and suggests that decreasing the temperature to 20°C could have clinical advantages.

Original languageEnglish
Pages (from-to)477-483
Number of pages7
JournalJournal of Oral Pathology and Medicine
Issue number5
Publication statusPublished - May 2018

Bibliographical note

© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


  • Antineoplastic Agents/adverse effects
  • Cell Survival/drug effects
  • Cold Temperature
  • Cryotherapy/methods
  • Dose-Response Relationship, Drug
  • Fluorouracil/adverse effects
  • Humans
  • In Vitro Techniques
  • Inflammation Mediators/metabolism
  • Interleukin-6/metabolism
  • Mouth Mucosa/cytology
  • Stomatitis/pathology
  • Time Factors
  • Tumor Necrosis Factor-alpha/metabolism


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