Willson C J, Flake G P, Sills R C, Kissling G E, Cesta M F
Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA Integrated Laboratory Systems, Inc, Research Triangle Park, NC, USA.
Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Vet Pathol. 2016 May;53(3):682-90. doi: 10.1177/0300985815603432. Epub 2015 Aug 28.
o-Nitroanisole is an intermediate in the manufacture of azo dyes. In a National Toxicology Program stop-exposure study,o-nitroanisole induced hyperplasia, papillomas, and papillary carcinomas in the urinary bladder of Fischer 344/N rats.o-Nitroanisole was investigated since occupational or environmental exposure to aniline and azo dyes is a risk factor for urinary bladder cancer in humans. The current study describes the morphology of urinary bladder neoplasms seen in rats with respect to those observed in humans. This study also evaluated immunohistochemical expression of the cell cycle-related proteins cyclin D1 and p53 and the differentiation markers cytokeratin 20 and uroplakin III in hyperplastic (n= 11) and neoplastic (n= 6 papillomas,n= 11 carcinomas) lesions of the urinary bladder epithelium from rats treated with o-nitroanisole and in normal (n= 6) urinary bladders from untreated rats. The tumors observed were more similar to the papillary type rather than the muscle-invasive type of urinary bladder cancer in humans. The preneoplastic and neoplastic lesions observed suggest progression from hyperplasia to papilloma to papillary carcinoma. With neoplastic progression (hyperplasia to papilloma to carcinoma), cyclin D1 immunoreactivity progressively increased in intensity, percentage of cells staining, and distribution. Overexpression of p53 was not found. Cytokeratin 20 staining decreased in superficial cells, while uroplakin III staining increased in intermediate and basal cells with progression from hyperplasia to carcinoma. The results are consistent with increased cell cycle dysregulation or proliferation (cyclin D1), decreased differentiation (cytokeratin 20), and abnormal differentiation (uroplakin III) as lesions progress toward malignancy.
邻硝基苯甲醚是制造偶氮染料的中间体。在一项国家毒理学计划的停止暴露研究中，邻硝基苯甲醚在Fischer 344/N大鼠的膀胱中诱发了增生、乳头状瘤和乳头状癌。对邻硝基苯甲醚进行研究是因为职业性或环境性接触苯胺和偶氮染料是人类膀胱癌的一个风险因素。本研究描述了大鼠膀胱肿瘤的形态，并与人类观察到的情况进行了比较。本研究还评估了细胞周期相关蛋白细胞周期蛋白D1和p53以及分化标志物细胞角蛋白20和uroplakin III在经邻硝基苯甲醚处理的大鼠膀胱上皮增生性病变（n = 11）和肿瘤性病变（n = 6个乳头状瘤，n = 11个癌）以及未处理大鼠的正常膀胱（n = 6）中的免疫组化表达。观察到的肿瘤更类似于人类乳头状型而非肌层浸润型膀胱癌。观察到的癌前病变和肿瘤性病变提示从增生发展为乳头状瘤再到乳头状癌。随着肿瘤进展（增生到乳头状瘤再到癌），细胞周期蛋白D1免疫反应性在强度、染色细胞百分比和分布上逐渐增加。未发现p53过表达。随着从增生到癌的进展，细胞角蛋白20在表层细胞中的染色减少，而uroplakin III在中层和基底细胞中的染色增加。结果表明，随着病变向恶性发展，细胞周期失调或增殖增加（细胞周期蛋白D1）、分化降低（细胞角蛋白20）以及分化异常（uroplakin III）。
