接触矽尘及电焊烟尘工人肺癌组织中p53基因的初步研究

为了从分子水平揭示矽尘与肺癌的关系，采用免疫组化和ＰＣＲ－ＳＳＣＰ法对３６例矽尘相关肺癌和６例电焊烟尘相关肺癌的抑癌基因ｐ５３的突变进行了研究。样品为石蜡包埋的肺肿瘤组织块，平均保存１３．４年。ＰＣＲ－ＳＳＣＰ分析显示，１８例病例中存在异常的电泳条带（２０处突变），占所测４２个样品的４２．９％，其中５０％的突变发生于第８外显子上（１０／２０）。以上发现有别于非职业性肺癌的基因突变谱。在非职业性肺癌中，第８外显子的突变频率介于１７．５％～２３．５％。尘肺相关肺癌基因突变的发生频率，在不同病理分类的肺癌中也与普通肺癌不同。在普通肺癌中，小细胞肺癌ｐ５３基因突变率最高（７０％），肺腺癌最低，为３３％。而本研究结果相反，肺腺癌最高，小细胞肺癌为最低，分别为５３．９％和３０．８％。免疫组织化学观察也显示了很高的ｐ５３突变体蛋白表达的发生率（４６．９％）。本研究仅做两例测序分析，意外地发现，探测到的两处点突变均发生于ｐ５３基因突变的非热点区，而且均发生于第１４４密码子上。基因突变谱的不同，显示矽尘、电焊烟尘中可能具有特异的致癌物和致癌机理。

A Preliminary Study on p53 Gene in Lung Cancer Tissues of Workers Exposed to Silica and Welding Fumes

Mutations of suppressor gene p53 was studied in 36 cases of silica related lung cancer and 6 cases of welding fume related lung cancer with immunohistochemical and PCR SSCP methods. Cancer tissues were embedded in paraffin and stored for 13.4 years in average. Results revealed that there was abnormal mobility shift of electrophoresis in 18 cases with 20 point mutations of 42 specimens tested, accounted for 42.9%, and 50% (10/20) of the mutations were clustered in exon 8. This finding differed from mutational spectrum of gene in non occupational lung cancer, in which mutation frequency of exon 8 ranged from 17.5% to 23.5%. Gene mutation frequency in varied pathological categories of pneumoconiosis related lung cancer also differed from that in common lung cancer. In the latter, the highest one was in small cell lung cancer (70%) and the lowest in adenocarcinoma (33%), but in the former, the highest in adenocarcinoma (53.9%) and the lowest in small cell lung cancer (30.8%). Immunohistochemical observations also showed a very high prevalence of p53 gene mutation expression (46.9%). Sequencing, which was determined in two cases of this study, revealed that two point mutations all occurred in non hotspot codon 144 of p53 gene. Difference in gene mutation spectrum suggests that there exist specific carcinogens and carcinogenesis in silica and welding fume related lung cancer.