Dietary fat and male sex increase histopathological changes in a mouse model of oral cancer

Abstract

Objective To compare the effects of dietary fat and sex on murine oral squamous cell carcinoma pathology. Materials and methods Male and female C57Bl/6 mice (36/sex) received a low‐fat (10 kcal%) or high‐fat (60 kcal%) diet. Water (control), vehicle, or 4‐nitroquinoline‐1‐oxide in vehicle (50 µg/ml) was provided for 17 weeks followed by 6 additional weeks of water. Oral lesion development was recorded weekly. Histopathologic changes in tongues were examined and T cells (CD3+), macrophages (CD68+), and neutrophils (Ly6+) were quantified. Results All 4‐nitroquinoline‐1‐oxide treated mice developed oral tumors. High‐fat diet exacerbated pathology, demonstrated by an increased final tumor burden (10.9 ± 4.5 vs 7.9 ± 2.5, mm/mouse, p < 0.05; high‐fat diet vs. low‐fat diet, respectively), and a greater histopathology score. When dietary groups were combined, 4‐nitroquinoline‐1‐oxide treated males displayed higher histopathology scores than females (4.2 ± 0.3 vs. 3.6 ± 0.2, respectively, p< 0.05). Lymphoid cell infiltration was greater in the 4‐nitroquinoline‐1‐oxide mouse tongues than controls: T cells (14.0 vs 0.96 cells/mm²), macrophages (3.6 vs 1.8 cells/mm²), and neutrophils (12.0 vs 0.38 cells/mm²). Conclusion High‐fat diet and male sex increased the pathology of 4‐nitroquinoline‐1‐oxide ‐induced oral cancer. Elevated lymphoid cell infiltration contributed to disease pathology.