Bernardini S, Pelin K, Peltonen K, Järventaus H, Hirvonen A, Neagu C, Sorsa M, Norppa H
Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
Mutat Res. 1996 Dec 12;361(2-3):121-7. doi: 10.1016/s0165-1161(96)90246-0.
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 microM and 32.9 for 500 [corrected] microM 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 microM 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 SCE 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 SEC 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.
在22名已知两种多态性谷胱甘肽S-转移酶（GST）即GSTT1和GSTM1基因型的人类供体的全血淋巴细胞培养物中，研究了1,3-丁二烯的代谢产物3,4-环氧丁烷-1,2-二醇（EBD）48小时处理对姐妹染色单体交换（SCE）的诱导作用。对于这两个基因，纳入了代表缺乏相应GST基因和同工酶的纯合“无效”基因型以及具有至少一个完整基因和GST活性的“阳性”基因型的供体。所有基因型组中SCE/细胞的平均频率相似：GSTT1无效（n = 10）（250μM EBD时平均为22.0，500μM[校正后]EBD时为32.9），GSTT1阳性（n = 14）（分别为21.3和34.6），GSTM1无效（n = 10）（20.3和33.5）以及GSTM1阳性供体（n = 15）（20.6和34.8）。在500μM EBD浓度下，所有供体的淋巴细胞培养物均显示复制指数显著降低。无论是单独还是联合分析，EDB诱导的SCE或复制指数的差异均与GSTM1和GSTT1基因型无关。当将EBD诱导的SCE与丁二烯的其他两种已知环氧化物代谢产物的诱导作用进行比较时，1,2:3,4-二环氧丁烷（DEB）在比EBD或1,2-环氧-3-丁烯（MEB）低两个数量级以上的浓度下才有效。结论是，EBD是培养的人淋巴细胞中SCE的有效诱导剂，尽管不如MEB有效，且明显不如DEB有效。与先前关于DEB和MEB的研究结果相反，多态性GSTM1和GSTT1似乎不参与人淋巴细胞中EBD的解毒过程。
