Genetic analyses of bronchogenic, carcinoma arising in ex-chromate workers : researches on sequential change of bronchial dysplastic changes and autopsy cases.

铬酸盐工人是肺癌的高危人群，为支气管癌的发生提供了良好的模型。我们研究了细胞周期调节蛋白（p53, MDM2, p21, p14, p16， cyclin D1和RB）在铬酸盐诱导的鳞状细胞癌（SCCs）中的免疫组织化学表达和杂合性缺失（LOH），并与非暴露个体的肺癌进行了比较。7例染色质诱导肺癌中，p53、MDM2、p21、p14、p16、cyclin D1、RB的异常表达率分别为71%、43%、100%、0%、71%、29%和0%。相比之下，来自非暴露个体的10个SCCs分别为80%，40%,100%,10%,60%，30%和20%。这些蛋白的表达频率在染色质诱导的SCCs和对照组之间没有显著性差异。然后，我们使用7种微卫星标记物：D3S1300 (3p), c131107 (3p), D5S644 (5q), D9S171(9p), mfd220 (9q), RBi2 （13q）和TP53(17p)，检测了7名铬酸盐暴露工人肺癌患者的LOH和10名没有铬酸盐暴露的比较病例。暴露于铬的工人中有6例是信息性的，而对照组中所有病例都是信息性的。铬酸盐暴露肿瘤中3p、3p、5q、9p、9q、13q和17p位点的LOH频率。与未接触铬酸盐的肿瘤无显著差异。这些发现表明，铬酸盐肺癌的致癌机制可能与非铬酸盐肺癌没有什么不同。

Chromate workers are well known to be a high-risk group for developing lung cancers and provide a good model for bronchial carcinogenesis. We investigated expression of cell cycle regulatory proteins (p53, MDM2, p21, p14, p16, cyclin D1 and RB) immunohistochemically and loss of heterozygosity (LOH) in chromate induced squamous cell carcinomas (SCCs), compared with those in lung cancers from nonexposed individuals. Of 7 chromate-induced lung cancer, abnormal expression of p53, MDM2, p21, p14, p16, cyclin D1 and RB were 71%, 43%, 100%, 0%, 71%, 29% and 0%, respectively. In contrast, of 10 SCCs from nonexposed individuals were 80%, 40%, 100%, 10%, 60%, 30% and 20%, respectively. The frequency of expression of these proteins proved to be not significant between chromate-induced SCCs and the comparison group. Then, we examined LOH in 7 lung cancers from chromate-exposed workers and in 10 comparison cases without chromate exposure, using 7 microsatellite markers : D3S1300 (3p), C13 1107 (3p), D5S644 (5q), D9S171(9p), mfd220 (9q), RBi2 (13q) and TP53(17p). The 6 cases out of chromate-exposed workers were informative, whereas all the cases were informative in the comparison group. The frequency of LOH at 3p, 3p, 5q, 9p, 9q, 13q and 17p loci in tumors with chromate exposure.was not significantly different from that in tumors without chromate exposure. These findings suggest that the carcinogenic mechanisms of chromate lung cancer may not differ from that of non-chromate lung cancer.