Molecular Analysis of p53 and K-Ras in Lung Carcinomas of Coal Miners

Details

• Personal Author:
  Li Y ; Sarkar FH ; Vallyathan V
• Description:
  Thirty-three cases of non-small cell lung cancers (NSCLC) from the archives of National Coal Workers' Autopsy Study were studied for mutational alterations in p53 and K-ras using PCR-SSCP, DNA sequencing and PCR-oligonucleotide probe hybridization techniques. Mutations of the p53 were observed in 4 smokers (19%) and one in a never smoker (8%). Two polymorphisms in smokers were detected at codon 213, a common site for sequence variation. Among the smokers the p53 mutations were in the heavy smokers. In never smokers there was only a single p53 mutation and two K-ras mutations. In never smokers the frequency of K-ras mutations was similar (17%) in smokers, but one never smoker had two K-ras mutations. Mutations of p53 were more frequent in adenocarcinomas (27%) and they were AT-->GC transitions. Four of 11 (36%) adenocarcinomas were found to have K-ras codon 12 mutations, and one adenocarcinoma had two K-ras mutations. There were two large cell undifferentiated carcinomas with p53 mutation and one with a K-ras mutation. Two of the 16 squamous cell carcinomas were positive for p53 mutation, while no K-ras mutations were found in this group. The results of these preliminary studies indicate a moderately different mutational spectrum of p53 and K-ras in coal miners independent of cigarette smoking. The mutational spectrum observed in this study of coal miners with heavy cigarette smoking history suggest a protective effect of coal mine dust in preventing abnormal mutations induced by chemical carcinogens in cigarette smoke or reactive oxygen species. These limited preliminary studies provide insight into the possibility of accurately measuring changes in etiologic markers to unravel the uncertainties of cancer in coal miners. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Air Pollution, Indoor Carcinogens Chemistry Coal Coal Mining Dust Environmental Monitoring Hazardous Substances Hypersensitivity Irritants Mining Occupational Health Particulate Matter Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety Smokers Tobacco Products Workplace

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• Keywords:
  Air-contamination Air-samples Airborne-dusts Airborne-particles Breathing Breathing-atmospheres Breathing-zone Carcinogenesis Chemical-analysis Chemical-hypersensitivity Chemical-properties Cigarette-smoking Coal-dust Coal-miners Coal-workers Dust-analysis Dust-exposure Exposure-assessment Particle-aerodynamics Particulate-dust Particulate-sampling-methods Particulates Respiratory-hypersensitivity Respiratory-irritants Respiratory-system-disorders Smoking Toxic-effects Work-environment Worker-health

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• ISSN:
  1107-3756
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Michigan ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  453-459
• Volume:
  8
• Issue:
  4
• NIOSHTIC Number:
  nn:20033196
• Citation:
  Int J Mol Med 2001 Oct; 8(4):453-459
• Contact Point Address:
  Dr. Fazlul H. Sarkar, Department of Pathology, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, MI 48201
• Email:
  fsarkar@med.wayne.edu
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  True
• Source Full Name:
  International Journal of Molecular Medicine
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:793490578d06c56037214dc2e244a4adc3685889a523b1259ead1344de901f10ceb54c3f95dc030bfbca493e60a6d1d61ebf0d220086c20f1f9f2b7119372913
• Download URL:
  https://stacks.cdc.gov/view/cdc/188867/cdc_188867_DS1.pdf
• File Type:
  [PDF - 2.11 MB ]