真菌霉素诱发的小鼠肺腺癌组织发生的研究

Histogenesis of lung adenocarcinoma induced by oral adminstration of mycotoxins in mice

目的 探讨真菌毒素诱发的NIH小鼠肺腺癌组织学来源及其可能致癌机理。方法 采用34例长期灌胃黄曲霉毒素G1(AFG1)和杂色曲霉素(ST)诱发的NIH小鼠实验性肺腺癌组织作为研究对象,同时以12例正常肺组织作为对照。采用免疫组化染色方法以肺Ⅱ型肺泡上皮细胞特异分化标志物SP C和Clara细胞特定分化标志物CC 10的表达情况确定肺腺癌的组织来源。同时以免疫组化方法分析本组实验性肺腺癌P5 3、Ras和PCNA的表达情况。结果 全部34例肺腺癌癌细胞均可见肺Ⅱ型肺泡上皮细胞特异分化标志物SP C蛋白的阳性表达,阳性表达率为10 .0 % ,而Clara细胞特定分化标志物CC 10均为阴性表达(P <0 .0 1)。肺腺癌细胞PCNA平均阳性标记指数为73 .32 % ,明显高于对照组2 2 . 4 3% (P <0 . 0 1) ,但肺腺癌细胞未见突变型抑癌基因P5 3和癌基因RasP2 1在蛋白水平上的表达。结论 真菌毒素诱发的实验动物肺腺癌组织来源于Ⅱ型肺泡上皮细胞,具有较高的增殖活性,但未见突变型P5 3和RasP2 1在蛋白水平的表达。

Objective To study the histogenesis and the putative mechanisms of adenocarcinoma induced by AFG1 and ST in NIH mice. Methods Thirty-four cases of lung adenocarcinomas induced by AFG1 and ST in NIH mice were included in this study and 12 cases of normal lung tissues were used as control. The phenotype of the lung adenocarcinomas was determined by immunohistochemical expression of SP-C and CC-10 at protein level. The expression of P53,Ras P21 and PCNA was studied with immunohistochemical staining. Result The positive expression of SP-C was found in all the lung adenocarcinomas, while no expression of CC-10 could be seen. The labelling index of PCNA in the adenocarcinomas were significantly higher than that of control(P<0.01). No positive expression of mutant P53 and Ras at protein level could be found. Conclusion The lung adenocarcinomas induced by the two mycotoxins in NIH mice arise from alveolar type Ⅱ cells and no expression of mutant P53 and Ras at protein level was found in the lung adenocarcinomas.