石棉及电焊烟尘相关肺癌组织K-ras基因突变的研究

为了解石棉及电焊烟尘相关肺癌的Ｋ－ｒａｓ基因突变情况，并与非职业肺癌的Ｋｒａｓ基因突变特点比较，进一步探讨石棉及电焊烟尘的致癌机理。收集８例非职业肺癌组织、９例石棉相关肺癌组织及４例电焊烟片段长度多态性分析，单链构象多态性分析及ＤＮＡ真接测序分析。

K-ras gene mutations of asbestos and welding-fumes related human lung cancer

To investigate the K-ras gene mutations in asbestos and welding-fumes related human lung cancer (hLC), comparing with the mutational spectrum of K-ras gene in non-occupational hLC, 8 cases of non-occupational hLC, 9 cases of asbestos-related hLC and 4 cases of welding-fumes related hLC were collected. The techniques of genomic DNA extraction, nested-polymerase chain reaction (PCR), polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and DNA direct sequencing were employed. The results: showed the mutation frequencies of K-ras gene were 25% in non-occupational hLC and welding-fumes related hLC, whereas 44.4% in asbestos-related hLC. Mutations mainly occurred in codons 12 and 15. A mutation of codon 13 was detected in welding-fumes related hLC. The type of base substitution was principally G-->T transversion in non-occupational hLC, whereas mainly G-->A transition in asbestos and welding-fumes related hLC. The results suggested there were obvious differences of K-ras gene mutations among non-occupational hLC, asbestos and silica related hLC. Therefore, different mechanisms of carcinogenesis were implicated among them. However, no speific spectrum of K-ras gene mutation can be derived from welding-fumes related hLC because of the limitation of samples.