Mutant c-Ki-ras p21 protein in chemical carcinogenesis in humans exposed to vinyl chloride.
DeVivo-I; Marion-J; Smith-SJ; Carney-WP; Brandt-Rauf-PW
Cancer Causes and Control 1994 May; 5(3):273-278
Immunohistochemistry was used to demonstrate the presence of Asp-13- p21-protein in liver angiosarcomas (ASLs) from vinyl-chloride (75014) (VC) exposed workers with corresponding mutations in tumor DNA. Additionally, serum immunoblotting was performed to investigate the presence of the protein in the serum of these cancer patients and in the serum of VC exposed workers without tumors. From a cohort of more than 400 workers employed in VC polymerization facilities in France since 1950, a sample of 60 of the most heavily exposed individuals was selected for further study. The sample population included five cases of ASL, one case of hepatocellular carcinoma, nine cases of benign angiomatous lesions of the liver, and 45 individuals with no evidence of neoplastic lesions of the liver. Allele specific oligonucleotide hybridization of DNA extracted from liver tumor samples showed that four of the five cases of ASL contained guanine to adenine transitions at the second base of codon 13 of the c-Ki-ras gene. Tumor tissue and serum from these patients were positive for the corresponding mutant protein. Serum samples from eight of the nine subjects with benign angiomatous lesions and from 22 of the subjects with no evidence of liver lesions were also positive for the mutant protein. Serum immunoblotting, however, for 28 age, gender, and race matched, unexposed controls were all negative. Stratification by years of VC exposure showed a significant linear trend for the occurrence of the mutant protein in serum with increasing duration of exposure. The authors suggest that detection in serum of the mutant p21 protein can be a valid surrogate for ras gene expression at the tissue level. Serum mutant p21 protein may be a useful molecular epidemiologic biomarker for the study of chemical carcinogenesis in humans exposed to VC and possibly for the study of other mutant ras related human cancers.
NIOSH-Publication; NIOSH-Grant; Polymerization; Protein-chemistry; DNA-damage; Carcinogens; Mutagenesis; Liver-cancer; Liver-damage; Biological-monitoring; Blood-serum; Genotoxic-effects
Environmental Sciences Columbia University Sch of PH 60 Haven Avenue/b-1 Level New York, NY 10032
Cancer Causes and Control
Columbia University New York, New York, New York