Effectiveness of radiotherapy+ozone on tumoral tissue and survival in tongue cancer rat model

Auris Nasus Larynx. 2018 Feb;45(1):128-134. doi: 10.1016/j.anl.2017.03.017. Epub 2017 Apr 6.


Objective: The objective of this study is to examine therapeutic effect of the combination of radiotherapy and ozone which features increasing of the destruction of cancer cells by increasing oxygen level of the body on advanced tongue cancer induced in rats.

Methods: A total of 36 female rats were included in this study as 4 groups. Group 1 (Cancer, n=8): 4NQO. Group 2 (Cancer+Radiotherapy, n=10): 4NQO+Radiotherapy. Group 3 (Cancer+Ozone+Radiotherapy, n=10): 4NQO+Ozone+Radiotherapy. Group 4 (Cancer+Ozone, n=10): 4NQO+Ozone. Group 5 (Control, n=8): Physiological saline solution. At the end of the week 20, rats in Groups 1 and 5 were sacrified. The rats in Groups 2,3 and 4 were waited until oral food intake was disrupted. The necessary applicatione were then carried out and survivals were evaluated. Each rat was sacrified after death. Tongues of the rats were excised, stained with hematoxylin & eosin and histopathologically evaluated.

Results: Histopathologic evaluation: The model that we applied was seen to achieve success in Group 1 in which 7 of the rats developed squamous cell carcinoma and one rat developed dysplasia at the end of the week 20. In Group 2 squamous cell cancer was seen in 6 and dysplasia in 4 rats. Six rats presented normal tongue tissues and 4 rats developed hyperplasia in Group 3. In Group 4; 3 rats had squamous cell cancer, 2 rats dysplasia, 3 rats hyperplasia and 2 rats had normal tissue. In Group 5, normal tongue tissues were observed in all rats. A significant histopathological improvement was observed in Group 3 compared to Group 2 (p<0.05). Histopathologic scorings were similar in Groups 3 and 5 (p>0.05). No statistically significant difference was found in histopathologic scorings between Group 1 and Group 2 (p>0.05). A significant improvement was observed in Group 4 compared to Group 1 (p<0.05). Group 3 showed a significant histologic improvement compared to Group 4 (p<0.05). Evaluation of survival: Survival times were found as 3.4±1.3 days, 76.4±14.9days and 76.4±14.9 days in the Groups 2, 3 and 4; respectively. Survival was significantly longer in Group 3 than in Groups 2 and 4 (p<0.05). Survival was significantly longer in Group 4 compared to Group 2 (p<0.05).

Conclusion: In this study, demonstrated that radiotherapy plus ozone application both provided histopathological improvement and prolonged survival in advanced tongue cancer rat model.

Keywords: 4-NQO; Histopathology; Ozone; Radiotherapy; Survival; Tongue cancer.

MeSH terms

  • 4-Nitroquinoline-1-oxide
  • Animals
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Combined Modality Therapy
  • Disease Models, Animal
  • Female
  • Ozone / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Tongue / pathology
  • Tongue Neoplasms / chemically induced
  • Tongue Neoplasms / drug therapy*
  • Tongue Neoplasms / pathology
  • Tongue Neoplasms / radiotherapy*


  • 4-Nitroquinoline-1-oxide
  • Ozone