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 six 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 < .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 < .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.

Keywords: 4-Nitroquinoline-1-oxide; high-fat diet; mouse model; oral cancer; oral squamous cell carcinoma.