Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Gene deletion of glutathione S-transferase theta: correlation with induced genetic damage and potential role in endogenous mutagenesis.

Authors
Wiencke-JK; Pemble-S; Ketterer-B; Kelsey-KT
Source
Cancer Epidemiol Biomark Prev 1995 Apr-May; 4(3):253-259
NIOSHTIC No.
20000996
Abstract
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.
Keywords
Mutagenesis; Humans; Butadienes; Genetics; DNA-damage
Contact
Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco 94143
CODEN
CEBPE4
CAS No.
106-99-0; 930-22-3
Publication Date
19950401
Document Type
Journal Article
Funding Amount
162000
Funding Type
Grant
Fiscal Year
1995
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-K01-OH-00110
Issue of Publication
3
ISSN
1055-9965
NIOSH Division
OD
Priority Area
Cancer
Source Name
Cancer Epidemiology, Biomarkers & Prevention
State
MA; CA
Performing Organization
Harvard University, School of Public Health, Occupational Health Program, Boston, Massachusetts
TOP