Analysis of K-ras and p53 mutations in mesotheliomas from humans and rats exposed to asbestos.
Malignant mesothelioma is known to be associated with asbestos exposure. However, the mechanism of mesothelial carcinogenesis in relation to the activation of proto-oncogenes or inactivation of tumor suppressor genes remains unclear. In this study, the PCR-Primer Introduced Restriction Site (PCR-PIRS) assay was employed to examine mutations in the K-ras proto-oncogene in mesothelioma tissues from workers exposed to asbestos and from rats treated with asbestos. Mutations in exons 5-8 of the p53 tumor suppressor gene were determined by direct DNA sequence analysis. Results of the PCR-PIRS analysis revealed no mutations in codons 12, 13 or 61 of the K-ras gene in any of the 17 human or 22 rat mesothelioma tissue samples. These results were confirmed by direct DNA sequence analysis. No mutations were found in exons 5-8 of the p53 gene in any of the mesothelioma tissue samples analyzed. These results and the results reported by others indicate that the K-ras proto-oncogene and p53 tumor suppressor gene may not play a critical role in the induction of mesothelioma by asbestos either in humans or in rats.
Ni
Z
Z
Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, Morgantown, WV 26505-2888, USA.
Liu
Y
Y
Keshava
N
N
Zhou
G
G
Whong
W
W
Ong
T
T
D000818:Animals; D001194:Asbestos / Q000009:adverse effects*; D001483:Base Sequence; D002273:Carcinogens / Q000009:adverse effects*; D004252:DNA Mutational Analysis; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced / Q000235:genetics*; D009154:Mutation; D016273:Occupational Exposure / Q000009:adverse effects; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D001194:Asbestos; D004262:DNA Restriction Enzymes