Carcinogen Macromolecular Adducts

Details

• Personal Author:
  Poirier MC ; Weston A
• Description:
  Carcinogen-macromolecular adducts are chemical modifications (`addition products') of nucleic acids and proteins that form in tissues and cells exposed to reactive chemical species. Significance of protein-adducts: The utility of proteins for human dosimetry in environmental and occupational chemical exposures was first demonstrated by the kinetic relationship between protein adduct persistence and protein lifetime. This important principle was established for hemoglobin modified by ethylene oxide or alkylating agents. It provided the basis for subsequent studies that investigated associations between carcinogen-protein adduct levels and carcinogen exposures. Protein adduct formation is a valuable surrogate for DNA adduct formation since many chemical carcinogens bind to both DNA and protein in blood with similar dose-response kinetics. In addition, blood proteins are available in large quantities, enhancing the feasibility of measuring carcinogen-protein adducts in human biomonitoring studies. Many protein adduct studies have considered exposures to different chemicals including ethylene, methylmethane sulfonate, BP, aflatoxin B1, 2-amino-3-methylimidazo[4,5-f]quinoline, dimethylnitrosamine, ethylene and propylene oxide, NNK and styrene. However, hemoglobin adducts formed through the metabolic activation of aromatic amines have proven to be excellent indicators of tobacco smoking. Tobacco smokers are readily distinguished from non-smokers, and a dose response has been observed between smokers of black tobacco containing high levels of 4-ABP and blonde tobacco containing low levels of 4-ABP. Protein adducts have been measured for twenty aromatic amines contained in cigarette smoke. The 3-aminobiphenyl-hemoglobin is a unique marker for passive smoking because 3-aminobiphenyl is present in side-stream but not main stream tobacco smoke. Hydroxyethylvaline in hemoglobin is also a dosimeter of tobacco smoking, but it is less specific because ethylene oxide has other environmental origins in addition to tobacco smoke. Although questions remain concerning the relationship between protein adduct levels and disease risk, measurement of protein adducts has been, and will continue to be, a valuable tool in molecular epidemiology studies. [Description provided by NIOSH]
• Subjects:
  Carcinogens Occupational Health Safety
• Keywords:
  Carcinogenicity DNA Adducts Molecular Epidemiology Nucleic Acids Proteins
• ISBN:
  9783540665274
• Publisher:
  Springer Verlag
• Document Type:
  Text
• Genre:
  Book
• Place as Subject:
  OSHA Region 3 ; 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:
  157-162
• NIOSHTIC Number:
  nn:20021412
• Citation:
  Encyclopedic reference of cancer. Schwab M, ed. Berlin: Springer Verlag, 2001 Dec; :157-162
• Editor(s):
  Schwab M
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  False
• Source Full Name:
  Encyclopedic reference of cancer
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8bf6bd9183647624292cf56e850660ccdf7a1f943a715ad54de7020acd502f7920f4fd62e507174120a3690c2d9fa3bff103a14f88bb943d899bd7cdd0e0f6ac
• Download URL:
  https://stacks.cdc.gov/view/cdc/198739/cdc_198739_DS1.pdf
• File Type:
  [PDF - 171.17 KB ]