Carcinogenesis, Vol 19, 377-380, Copyright © 1998 by Oxford University Press
S Bernardini, A Hirvonen, K Pelin and H Norppa
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.
ARTICLES
Induction of sister chromatid exchange by 1,2-epoxy-3-butene in cultured human lymphocytes: influence of GSTT1 genotype
Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki.
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