A High Fat Diet Augments 4NQO‐induced Oral Squamous Cell Carcinoma in Mice
Authors: Pytynia Matthew , Meyer Alice , Nguyen Andrew , Goral Joanna , Green Jacalyn M , Jham Bruno , Pitstick Lenore , Ciancio Mae J 
Published: November 2023

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide, and is more common in men than women. Since the diagnosis of HNSCC is typically late in disease progression, the prognosis is often poor, with significant co‐morbid effects. Common risk factors include tobacco exposure, alcohol use, and human papilloma virus infection. Effects of a high fat diet (HF) on oral cancer development and severity have not been clearly defined. The purpose of this study was to compare the effects of a high saturated fat diet and a low saturated fat diet on the induction and severity of oral SCC using a mouse model of 4‐nitroquinoline 1‐oxide (4NQO) induced SCC. We hypothesized that HF would augment 4NQO‐induced SCC when compared to the LF diet.

Materials and methods

Male (n=36) and female (n=36) C57Bl/6 mice (Jackson Labs), 5 weeks old, were equally distributed into a low fat (10kcal% fat; LF) or HF (60 kcal% fat) diet. Within each dietary group, mice were randomly assigned to one of 3 water treatment groups for 17 weeks: water alone (control); propylene glycol in water (1.25%; PG‐H2O); or 4NQO in PG‐H2O (50 μg/ml; 4NQO). After 17 weeks, all mice were given water alone for 6 weeks prior to euthanasia. Initial and weekly body weights were measured. Weekly assessments of the oral cavity began after 5 weeks and continued for the remaining 18 weeks. The presence of oral lesions, their size, and location were monitored and recorded weekly. Statistically significant differences in body weight, tumor size and severity were determined by ANOVA, p<0.05.

Results

All 4‐NQO treated mice developed tumors in the oral cavity; no control mice developed oral tumors. Overall tumor burden at 23 weeks for both sexes combined was statistically higher in the HF mice compared to the LF group (10.3±1.1 vs. 7.9±0.6, p=0.055). There was no significant difference in tumor burden as a result of gender. Significant changes in weekly body weights were determined, with 4NQO mice demonstrating lower final body weights than the H2O control group and the PG‐H2O control mice on the respective diets (p<0.05). Twenty‐four hour food intake was determined at week 19, demonstrating a significant reduction in calorie intake in the 4‐NQO male mice (p<0.05).

Conclusion

This mouse model of SCC, initially established to mimic the effects of smoking, demonstrated significantly greater tumor burden as a consequence of elevated fat intake. The contributory effects of HF associated metabolic and inflammatory changes in SCC development can be discerned using this model. The clinical implication of these findings may be helpful in modifying lifestyle to improve outcomes.

Support or Funding Information

Acknowledgements: Andrew Nguyen was supported by the Midwestern University Biomedical Sciences Program. We also recognize the Midwestern University Deans of CDMI and the Basic Science Division for their support of this research.