Wolf D C, Gross E A, Lyght O, Bermudez E, Recio L, Morgan K T
Chemical Industry Institute of Toxicology (CIIT), Research Triangle Park, North Carolina 27709, USA.
Toxicol Appl Pharmacol. 1995 May;132(1):27-35. doi: 10.1006/taap.1995.1083.
Mutation of the p53 tumor suppressor gene is a common event in many human cancers and has been specifically associated with invasive squamous cell carcinoma of the human skin and respiratory tract. Alterations in the p53 gene have also been identified in certain rodent tumors, including formaldehyde-induced nasal squamous cell carcinomas. Overexpression of transforming growth factor-alpha (TGF-alpha) is associated with carcinomas of the head and neck and respiratory tract in human patients and formaldehyde-induced rat nasal squamous cell carcinomas. Sections of rat noses containing tumors and other formaldehyde-induced lesions from rats exposed to 15 ppm formaldehyde vapor were examined using immunohistochemical techniques to detect and identify potential relationships between the presence and distribution of p53, proliferating cell nuclear antigen (PCNA), and TGF-alpha proteins. The five tumors that had p53 mutations were for mutant p53 protein by immunohistochemistry and three of six tumors with no detected p53 mutations were also immunoreactive for p53 protein. The presence, pattern, and distribution of p53 staining in tissue sections depended on the morphology of the lesion. PCNA immunoreactivity was strikingly similar in pattern and distribution to p53 immunoreactivity. The pattern and distribution of immunoreactivity for TGF-alpha did not directly correlate with the other markers. Mutation of the p53 tumor suppressor gene may be an important step in the progression of formaldehyde-induced nasal carcinogenesis in the rat. This study demonstrated that immunohistochemistry is a useful tool for the identification of sites within tumors that might have p53 mutations.
p53肿瘤抑制基因的突变在许多人类癌症中是常见事件，并且已特别与人类皮肤和呼吸道的浸润性鳞状细胞癌相关。在某些啮齿动物肿瘤中也已鉴定出p53基因的改变，包括甲醛诱导的鼻鳞状细胞癌。在人类患者以及甲醛诱导的大鼠鼻鳞状细胞癌中，转化生长因子-α（TGF-α）的过表达与头颈部和呼吸道的癌症相关。使用免疫组织化学技术检查了来自暴露于15 ppm甲醛蒸气的大鼠的含有肿瘤和其他甲醛诱导病变的鼻组织切片，以检测和鉴定p53、增殖细胞核抗原（PCNA）和TGF-α蛋白的存在与分布之间的潜在关系。通过免疫组织化学检测到具有p53突变的五个肿瘤中有突变型p53蛋白，并且六个未检测到p53突变的肿瘤中有三个对p53蛋白也具有免疫反应性。组织切片中p53染色的存在、模式和分布取决于病变的形态。PCNA免疫反应性在模式和分布上与p53免疫反应性惊人地相似。TGF-α免疫反应性的模式和分布与其他标志物没有直接相关性。p53肿瘤抑制基因的突变可能是大鼠甲醛诱导的鼻癌发生进展中的重要一步。这项研究表明，免疫组织化学是鉴定肿瘤内可能存在p
