Induction of sister chromatid exchange by 1,2-epoxy-3-butene in cultured human lymphocytes: influence of GSTT1 genotype. 1998

S Bernardini, and A Hirvonen, and K Pelin, and H Norppa
Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki.

The influence of glutathione S-transferase T1 (GSTT1) genotype on the genotoxicity of 1,2-epoxy-3-butene (MEB), a metabolite of 1,3-butadiene, was assessed by the analysis of sister chromatid exchanges (SCEs) in 72-h human whole-blood lymphocyte cultures. The cultures were from 18 donors, representing both GSTT1 'positive' genotype (with at least one undeleted GSTT1 allele; GSTT1 activity present) and GSTT1 'null' genotype (homozygous deletion of the GSTT1 gene; no GSTT1 activity). As we have previously observed that allelism of glutathione S-transferase M1 (GSTM1) affects SCE induction by MEB in cultured lymphocytes, only individuals with the GSTM1 null genotype were included in this study. At 125 and 250 microM MEB (treatment at 24 h for 48 h), the mean frequencies of MEB-induced SCEs per cell (control level subtracted) were 4.5 (SD 1.8) and 8.9 (SD 1.0) for GSTT1 positive cell cultures (n = 13) and 5.3 (SD 1.2) and 12.5 (SD 1.1) for GSTT1 null cell cultures (n = 5) respectively, and the difference between the genotypes was statistically significant (P < 0.001) at the higher dose. All individual mean frequencies of SCEs induced by 250 microM MEB were higher in the GSTT1 null group (range 11.2-13.9) than in the GSTT1 positive group (range 7.2-10.8). The findings suggest that GSTT1, in addition to GSTM1, is involved in the detoxification of MEB in human whole-blood lymphocyte cultures. The deletion of the GSTT1 gene results in reduced erythrocytic detoxification capacity, thereby increasing the genotoxic effects of MEB.

UI MeSH Term Description Entries
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004852 Epoxy Compounds Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS. Epoxide,Epoxides,Epoxy Compound,Oxiranes,Compound, Epoxy,Compounds, Epoxy
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D005982 Glutathione Transferase A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite. Glutathione S-Alkyltransferase,Glutathione S-Aryltransferase,Glutathione S-Epoxidetransferase,Ligandins,S-Hydroxyalkyl Glutathione Lyase,Glutathione Organic Nitrate Ester Reductase,Glutathione S-Transferase,Glutathione S-Transferase 3,Glutathione S-Transferase A,Glutathione S-Transferase B,Glutathione S-Transferase C,Glutathione S-Transferase III,Glutathione S-Transferase P,Glutathione Transferase E,Glutathione Transferase mu,Glutathione Transferases,Heme Transfer Protein,Ligandin,Yb-Glutathione-S-Transferase,Glutathione Lyase, S-Hydroxyalkyl,Glutathione S Alkyltransferase,Glutathione S Aryltransferase,Glutathione S Epoxidetransferase,Glutathione S Transferase,Glutathione S Transferase 3,Glutathione S Transferase A,Glutathione S Transferase B,Glutathione S Transferase C,Glutathione S Transferase III,Glutathione S Transferase P,Lyase, S-Hydroxyalkyl Glutathione,P, Glutathione S-Transferase,Protein, Heme Transfer,S Hydroxyalkyl Glutathione Lyase,S-Alkyltransferase, Glutathione,S-Aryltransferase, Glutathione,S-Epoxidetransferase, Glutathione,S-Transferase 3, Glutathione,S-Transferase A, Glutathione,S-Transferase B, Glutathione,S-Transferase C, Glutathione,S-Transferase III, Glutathione,S-Transferase P, Glutathione,S-Transferase, Glutathione,Transfer Protein, Heme,Transferase E, Glutathione,Transferase mu, Glutathione,Transferase, Glutathione,Transferases, Glutathione
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D012854 Sister Chromatid Exchange An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in BLOOM SYNDROME. Chromatid Exchange, Sister,Chromatid Exchanges, Sister,Exchange, Sister Chromatid,Exchanges, Sister Chromatid,Sister Chromatid Exchanges

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