title: Analysis of K-ras and p53 mutations in mesotheliomas from humans and rats exposed to asbestos.
abstract: 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.
authors.affiliation: Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, Morgantown, WV 26505-2888, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Ni
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: N
authors.initials: N
authors.lastname: Keshava
authors.forename: G
authors.initials: G
authors.lastname: Zhou
authors.forename: W
authors.initials: W
authors.lastname: Whong
authors.forename: T
authors.initials: T
authors.lastname: Ong
mesh_terms: 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
chemical_list: D002273:Carcinogens; D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D001194:Asbestos; D004262:DNA Restriction Enzymes