MUTAGENICITY OF BUTADIENE AND ITS EPOXIDE METABOLITES .1. MUTAGENIC POTENTIAL OF 1,2-EPOXYBUTENE, 1,2,3,4-DIEPOXYBUTANE AND 3,4-EPOXY-1,2-BUTANEDIOL IN CULTURED HUMAN LYMPHOBLASTS
MUTAGENICITY OF BUTADIENE AND ITS EPOXIDE METABOLITES .1. MUTAGENIC POTENTIAL OF 1,2-EPOXYBUTENE, 1,2,3,4-DIEPOXYBUTANE AND 3,4-EPOXY-1,2-BUTANEDIOL IN CULTURED HUMAN LYMPHOBLASTS
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DOI：
10.1093/carcin/15.4.713
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发表时间：
1994-04-01
期刊：
影响因子：
4.7
通讯作者：
SKOPEK, TR
中科院分区：
文献类型：
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作者：
COCHRANE, JE;SKOPEK, TR
在 TK6 人淋巴母细胞中的 tk 和 hprt 位点处测量了丁二烯 (BD) 环氧化物代谢物的致突变潜力。将TK6细胞暴露于0-400μM 1,2-环氧丁烯(EB)、0-800μM 3,4-环氧-1,2-丁二醇(EBD)或0-6μM 1,2,3,4-二环氧丁烷(DEB)24小时。让处理过的细胞生长几天，然后接种到含有 6-硫鸟嘌呤或三氟胸苷的培养基中，分别选择 hprt(-) 或 tk(-/-) 突变体。三种代谢物在两个位点均具有诱变性，DEB 在比 EB 或 EBD 低约 100 倍的浓度下表现出活性。在hprt位点，通过用3.5μM DEB、150μM EB和450μM EBD处理产生了5x10(-6)的诱导突变频率（大约是背景hprt(-)频率的两倍）。在tk位点，用1.0μM DEB、100μM EB和350μM EBD处理产生类似的突变频率(总tk(-/-)频率)增加。每种测试的环氧化物都能够诱导缓慢生长的 tk(-/-) 突变体。正如之前其他人所表明的，这种突变表型是由于 tk 区域发生巨大改变而导致的，这种改变完全消除了活性 tk 等位基因。此外，Southern印迹分析表明，大约一半的DEB诱导的hprt(-)突变体表现出野生型hprt限制性片段的丢失。没有观察到 EB 突变体中 hprt 缺失比例有统计学上的显着增加。 DEB 诱导缺失的能力可能与其形成 DNA-DNA 和 DNA-蛋白质交联的能力有关。
The mutagenic potential of the epoxide metabolites of butadiene (BD) was measured at the tk and hprt loci in TK6 human lymphoblastoid cells. TK6 cells were exposed for 24 h to 0-400 mu M 1,2-epoxybutene (EB), 0-800 mu M 3,4-epoxy-1,2-butanediol (EBD), or 0-6 mu M 1,2,3,4-diepoxybutane (DEB). Treated cells were allowed to grow for several days and then seeded in medium containing either 6-thioguanine or trifluorothymidine to select for hprt(-) or tk(-/-) mutants, respectively. Ah three metabolites were mutagenic at both loci, with DEB exhibiting activity at concentrations approximately 100-fold lower than EB or EBD. At the hprt locus, an induced mutation frequency of 5x10(-6) (approximately twice background hprt(-) frequency) was produced by treatment with 3.5 mu M DEB, 150 mu M EB and 450 mu M EBD. At the tk locus, a similar increase in mutation frequency (total tk(-/-) frequency) was produced by treatment with 1.0 mu M DEB, 100 mu M EB and 350 mu M EBD. Each epoxide tested was capable of inducing slow growth tk(-/-) mutants. This mutant phenotype, as shown previously by others, results from large alterations in the tk region which completely remove the active tk allele. In addition, Southern blot analysis revealed that approximately half of DEB-induced hprt(-) mutants displayed loss of wild-type hprt restriction fragments. No statistically significant increase in the fraction of hprt deletions among EB mutants was observed. The ability of DEB to induce deletions may be related to its ability to form DNA-DNA and DNA-protein cross-links.