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

Abstract

To compare the effects of dietary fat and sex on murine oral squamous cell carcinoma pathology. Male and female C57Bl/6 mice (36/sex) received a low-fat (10kcal%) or high-fat (60kcal%) diet. Water (control), vehicle, or 4-nitroquinoline-1-oxide in vehicle (50μg/ml) was provided for 17weeks 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. 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. 0.96cells/mm2 ), macrophages (3.6 vs. 1.8cells/mm2 ), and neutrophils (12.0 vs. 0.38cells/mm2 ). 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.