D'Agostini F, Fiallo P, Di Marco C, De Flora S
Institute of Hygiene and Preventive Medicine, University of Genoa, Italy.
Cancer Lett. 1994 Nov 11;86(2):167-75. doi: 10.1016/0304-3835(94)90075-2.
Skin lesions induced by exposure of three strains of female hairless mice to the light emitted by uncovered halogen quartz lamps were subjected to histopathological analysis. We examined 170 representative specimens out of a total of 597 skin lesions, i.e. 38 out of 74 SKH-1 mice, 110 out of 472 MF-1 mice, and 42 out of 51 C3H mice. The results provided evidence of various types of alterations, including preneoplastic changes, such as epidermal hyperplasia, and benign tumours, such as papillomas, as well as tumours with an increasing degree of malignancy, i.e., keratoacanthoma-like tumours, appendage/basal tumours, actinic keratoses/carcinomas in situ, and squamocellular carcinomas. SKH-1 was the most sensitive strain to the far-ultraviolet wavelengths delivered by halogen lamps, as shown not only by the shortest latency time and the highest multiplicity of skin lesions but also by the highest frequency of malignant tumours. Some areas of atypical melanocyte proliferation were only detected in C3H pigmented mice. Eighty-two of the lesions excised from MF-1 mice were additionally examined for p53 protein by immunohistochemical methods. Formalin-fixed, paraffin-embedded sections and frozen sections were analyzed in parallel by using polyclonal CM-1 antibody and monoclonal PAb240 antibody, respectively. A positive response for p53 was only observed in squamocellular carcinomas, and was related to the size of cancers; in fact, six out of 10 cancers of 10-30 mm in diameter were positive, whereas all 16 cancers of 2-9 mm in diameter were negative. All six positive squamocellular carcinomas were detected by using the CM-1 antibody, which recognizes both wild-type and mutant forms of p53 protein, and five of them were also positive with the PAb 240 antibody, which only recognizes the mutant form. Thus, p53 mutation appears to be a late event in the development of halogen-induced skin tumours in hairless mice, requiring a severe degree of malignancy and an advanced stage of the neoplastic mass growth.
将三株雌性无毛小鼠暴露于未加防护的卤素石英灯发出的光线下，由此诱发的皮肤损伤进行了组织病理学分析。在总共597处皮肤损伤中，我们检查了170个代表性样本，即74只SKH - 1小鼠中的38只，472只MF - 1小鼠中的110只，以及51只C3H小鼠中的42只。结果表明存在各种类型的改变，包括癌前变化，如表皮增生，以及良性肿瘤，如乳头状瘤，还有恶性程度不断增加的肿瘤，即角化棘皮瘤样肿瘤、附属器/基底肿瘤、光化性角化病/原位癌，以及鳞状细胞癌。SKH - 1是对卤素灯发出的远紫外线波长最敏感的品系，这不仅体现在最短的潜伏期和最高的皮肤损伤多样性上，还体现在恶性肿瘤的最高发生率上。仅在C3H有色小鼠中检测到一些非典型黑素细胞增殖区域。另外，对从MF - 1小鼠切除的82处损伤采用免疫组化方法检测p53蛋白。分别使用多克隆CM - 1抗体和单克隆PAb240抗体，对福尔马林固定、石蜡包埋切片和冰冻切片进行平行分析。仅在鳞状细胞癌中观察到p53阳性反应，且与癌症大小有关；实际上，直径10 - 30毫米的10处癌症中有6处呈阳性，而直径2 - 9毫米的16处癌症均为阴性。所有6例阳性鳞状细胞癌均通过使用识别p53蛋白野生型和突变型的CM - 1抗体检测到，其中5例使用仅识别突变型的PAb 240抗体也呈阳性。因此，p53突变似乎是无毛小鼠中卤素诱导的皮肤肿瘤发生发展过程中的一个晚期事件，需要高度恶性和肿瘤块生长的晚期阶段。
