Gene Deletion of Glutathione S-Transferase Theta: Correlation with Induced Genetic Damage and Potential Role in Endogenous Mutagenesis

Details

• Personal Author:
  Kelsey KT ; Ketterer B ; Pemble S ; Wiencke JK
• Description:
  Genetic traits that confer increased susceptibility to DNA and chromosomal damage from reactive epoxide and peroxides could be important individual risk factors in the development of human cancers. To provide an index of individual sensitivity to epoxides, we previously studied sister chromatid exchange (SCE) induction in peripheral blood lymphocytes and identified a trait involving sensitivity to chromosomal damage by monoepoxybutene and diepoxybutane (DEB), both potential carcinogenic metabolites of 1,3-butadiene. Individuals sensitive to DEB induction of SCEs also had an increased number of background or "spontaneous" SCEs. The present investigation was conducted to test whether a newly described deletion polymorphism in the glutathione S-transferase class theta (GSTT1) was significantly associated with the previously described inherited chromosomal sensitivity to DEB. The background and DEB-induced SCE frequencies in peripheral blood lymphocytes from 78 healthy volunteers were determined with the use of fluorescence plus Giemsa staining. The presence or absence of the homozygous deletion of the GSTT1 gene was determined for each participant using PCR methods. In the present study, we report a close correlation of the DEB sensitivity trait with the novel polymorphism in GSTT1. The GSTT1 polymorphism was also highly associated with the background frequencies of SCE. These studies raise the possibility that DBE is a substrate for GST-theta. Individuals who carry a homozygous deletion of the GSTT1 gene may be at increased risk for genotoxic damage from environmental or occupational 1,3-butadiene exposures. The association of the GSTT1 deletion polymorphism with increases in background SCEs indicates that substrates for this isozyme are encountered commonly in the environment or are endogenous in nature. [Description provided by NIOSH]
• Subjects:
  Butadienes DNA Genetics Mutagens Occupational Health Safety
• Keywords:
  DNA-damage Humans Mutagenesis
• ISSN:
  1055-9965
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Massachusetts ; OSHA Region 1 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OD - Office of the Director
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  253-259
• Volume:
  3
• Issue:
  3
• NIOSHTIC Number:
  nn:20000996
• Citation:
  Cancer Epidemiol Biomark Prev 1995 Apr-May; 4(3):253-259
• Contact Point Address:
  Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco 94143
• CAS Registry Number:
  1,3-Butadiene (CAS RN 106-99-0) ; Vinyloxirane (CAS RN 930-22-3)
• Federal Fiscal Year:
  1995
• Performing Organization:
  Harvard University, School of Public Health, Occupational Health Program, Boston, Massachusetts
• Peer Reviewed:
  True
• Start Date:
  19910930
• Source Full Name:
  Cancer Epidemiology, Biomarkers & Prevention
• End Date:
  19940929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:75edbee3e14326172ff6aeaa6c1d2e60d3c6fbc432328440bf75b323ad8086b90c468ab07fc0394c30bdb1fbe39e2d3a629d41d72633a330dafcf819064f1e28
• Download URL:
  https://stacks.cdc.gov/view/cdc/198288/cdc_198288_DS1.pdf
• File Type:
  [PDF - 1.31 MB ]