Mutant c-Ki-ras p21 protein in chemical carcinogenesis in humans exposed to vinyl chloride

Details

• Personal Author:
  Brandt-Rauf PW ; Carney WP ; DeVivo I ; Marion J ; Smith SJ
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Carcinogens Digestive System Digestive System Diseases DNA Liver Mutagens Neoplasms Occupational Health Polymers Safety
• Keywords:
  Biological-monitoring Blood-serum DNA-damage Genotoxic-effects Liver-cancer Liver-damage Mutagenesis NIOSH-Grant NIOSH-Publication Polymerization Protein-chemistry

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• ISSN:
  0957-5243
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  273-278
• Volume:
  5
• Issue:
  3
• NIOSHTIC Number:
  nn:00223217
• Citation:
  Cancer Causes Control 1994 May; 5(3):273-278
• Contact Point Address:
  Environmental Sciences Columbia University Sch of PH 60 Haven Avenue/b-1 Level New York, NY 10032
• CAS Registry Number:
  Vinyl chloride (CAS RN 75-01-4)
• Federal Fiscal Year:
  1994
• Performing Organization:
  Columbia University New York, New York, New York
• Peer Reviewed:
  True
• Start Date:
  19890715
• Source Full Name:
  Cancer Causes and Control
• End Date:
  19930114
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:bd2e022675aba6043af727c048f61d24e38fa72d11a2c053279b184b3f3d17185820fa16429982f41e2760c9d9b6a503e457256a37eed32a7633fad7481b24d7
• Download URL:
  https://stacks.cdc.gov/view/cdc/205167/cdc_205167_DS1.pdf
• File Type:
  [PDF - 2.59 MB ]