[Evidence on the carcinogenicity of silica at DNA level in human]

The alteration of p53 and K-ras gene in 36 lung cancers of workers occupationally exposed to silica (LCWS) was studied. DNA was extracted from paraffin\|embedded tissues and amplified by PCR. PCR-SS-CP analysis on exons 5, 7 and 8 of p53 gene revealed that 43.8% of mutations were clustered in exon 8 of p53 gene. In ordinary lung cancer, the mutation rate of exon 8 was fluctuated around 20%. The prevalence of mutations was the highest (70%) in small cell lung cancer (SCLC) and the lowest in adenocarcinoma(33%). In our study the mutation rate was high in adenocarcinoma(53.9%) and low in SCLC (30.8%). The K-ras gene of LCWS also revealed a different mutation pattern. Unexpectedly, no mutation was found at codon 12 in 36 LCWS by PCR-RFLP, which is the predominant mutation in K-ras gene in ordinary lung cancer. The point mutation study by DNA sequencing confirmed the absence of codon 12 mutation in K-ras gene in LCWS. The mutations observed in this study were frequently distributed in codons 13 and 15, principally a G-C transversion, instead of G-T transversion in ordinary lung cancer.