Department of Biochemistry and Molecular Genetics, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA.
Department of Anatomy, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA.
Oral Dis. 2024 May;30(4):1989-2003. doi: 10.1111/odi.14728. Epub 2023 Sep 20.
To investigate the effects of dietary folate and sex on histopathology of oral squamous cell carcinoma in mice.
Mice (C57Bl/6, 30/sex) were fed either a deficient folate or sufficient folate diet. Vehicle or 4-nitroquinoline1-oxide (50 μg/mL) in vehicle were administered in drinking water for 20 weeks, followed by 6 weeks of regular drinking water. Oral lesions were observed weekly. Tongues were studied for histopathologic changes. Immunohistochemical techniques were used to measure cell proliferation (Ki67+), and to quantify expression of folate receptor, reduced folate carrier, and proton-coupled folate transporter. T cells, macrophages, and neutrophils were counted and normalized to area.
All 4NQO-treated mice developed oral tumors. Dietary folate level did not affect tumor burden. More tumors were observed on the ventral aspect of the tongue than in other locations within the oral cavity. 4-nitroquinoline-1-oxide-treated mice displayed 27%-46% significantly lower expression of all three folate transport proteins; diet and sex had no effect on folate transporter expression. T-cell and neutrophil infiltration in tongues were 9.1-fold and 18.1-fold increased in the 4-nitroquinoline-1-oxide-treated mouse tongues than in controls.
Treatment with 4NQO was the primary factor in determining cancer development, decreased folate transport expression, and lymphoid cell infiltration.
研究饮食叶酸和性别对小鼠口腔鳞状细胞癌组织病理学的影响。
将 C57Bl/6 小鼠（30 只/性别）分别喂食叶酸缺乏或充足的饮食。用含或不含 4-硝基喹啉 1-氧化物（50μg/mL）的饮用水进行为期 20 周的处理，随后用普通饮用水处理 6 周。每周观察口腔病变。研究舌组织的病理变化。采用免疫组织化学技术测量细胞增殖（Ki67+），并定量检测叶酸受体、还原叶酸载体和质子偶联叶酸转运蛋白的表达。计算 T 细胞、巨噬细胞和嗜中性粒细胞的数量，并与面积进行归一化。
所有接受 4NQO 处理的小鼠均发生口腔肿瘤。饮食叶酸水平并不影响肿瘤负担。与口腔其他部位相比，舌的腹侧面观察到的肿瘤更多。4-硝基喹啉-1-氧化物处理的小鼠三种叶酸转运蛋白的表达显著降低 27%-46%；饮食和性别对叶酸转运蛋白的表达没有影响。与对照组相比，4-硝基喹啉-1-氧化物处理的小鼠舌部 T 细胞和嗜中性粒细胞浸润分别增加了 9.1 倍和 18.1 倍。
4NQO 的处理是决定癌症发生、降低叶酸转运蛋白表达和淋巴细胞浸润的主要因素。
