Induction of sister chromatid exchange by 3,4-epoxybutane- 1,2-diol in cultured human lymphocytes of different GSTT1 and GSTM1 genotypes

Abstract

The induction of sister chromatid exchanges (SCEs) by a 48-h treatment with 3,4-epoxybutane-1,2-diol (EBD), a metabolite of 1,3-butadiene, was studied in whole-blood lymphocyte cultures of 22 human donors with known genotypes of two polymorphic glutathione S-transferases (GSTs), GSTT1 and GSTM1. For both genes, donors representing a homozygous ‘null’ genotype lacking the respective GST gene and isozyme and a ‘positive’ genotype with at least one intact gene and GST activity were included. The mean frequencies of SCE/cell were similar in all genotype groups: GSTT1 null (n = 10) (mean 22.0 for 250 μM and 32.9 for 250 500 μM of EBD), GSTT1 positive (n = 14) (21.3 and 34.6, respectively), GSTM1 null (n = 10) (20.3 and 33.5) and GSTM1 positive donors (n = 15) (20.6 and 34.8). At 500 μM concentration of EBD, the lymphocyte cultures of all donors showed a significantly decreased replication index. No differences in EDB-induced SCEs or in replication index could be associated with the GSTM1 and GSTT1 genotypes either separately or in combination. When SCEs induction by EBD was compared to that of two other known epoxide metabolites of butadiene, 1,2:3,4-diepoxybutane (DEB) was effective at concentrations over two orders of magnitude lower than EBD or 1,2-epoxy-3-butene (MEB). It is concluded that EBD is an efficient inducer of SCE in cultured human lymphocytes, although not quite as effective as MEB and clearly less effective than DEB. Contrary to previous findings with DEB and MEB, the polymorphic GSTM1 and GSTT1 do not appear to be involved in the detoxification of EBD in human lymphocytes.