为了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，选择C57Bl/6小鼠（30只/性别），分别喂养叶酸缺乏或叶酸充足的饮食。在饮用水中添加车辆或4-硝基喹啉1-氧化物（50μg/mL）溶液，连续供应20周，并随后饮用正常饮用水6周。每周观察口腔病变。对舌部进行组织病理学研究。采用免疫组织化学技术测量细胞增殖（Ki67+）并定量叶酸受体、还原型叶酸载体以及质子耦合型叶酸转运蛋白的表达。用T细胞、巨噬细胞和中性粒细胞计数并标准化到面积。所有接受4-硝基喹啉1-氧化物处理的小鼠都出现口腔肿瘤。饮食中的叶酸水平并不影响肿瘤负荷。舌腹侧比口腔其他位置观察到更多的肿瘤。接受4-硝基喹啉1-氧化物处理的小鼠，其三种叶酸转运蛋白的表达量降低了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，接受4-硝基喹啉1-氧化物处理的小鼠舌部的T细胞和中性粒细胞浸润分别增加了9.1倍和18.1倍。4-硝基喹啉1-氧化物的处理是决定癌症发展、叶酸转运蛋白表达降低以及淋巴细胞浸润的主要因素。 © 2023 Wiley Periodicals LLC.

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.© 2023 Wiley Periodicals LLC.