MUTAGENICITY OF BUTADIENE AND ITS EPOXIDE METABOLITES .2. MUTATIONAL SPECTRA OF BUTADIENE, 1,2-EPOXYBUTENE AND DIEPOXYBUTANE AT THE HPRT LOCUS IN SPLENIC T-CELLS FROM EXPOSED B6C3F1 MICE
MUTAGENICITY OF BUTADIENE AND ITS EPOXIDE METABOLITES .2. MUTATIONAL SPECTRA OF BUTADIENE, 1,2-EPOXYBUTENE AND DIEPOXYBUTANE AT THE HPRT LOCUS IN SPLENIC T-CELLS FROM EXPOSED B6C3F1 MICE
复制标题
DOI：
10.1093/carcin/15.4.719
复制
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：
--
作者：
COCHRANE, JE;SKOPEK, TR
本文测定了丁二烯(BD)、1，2-环氧丁烯(EB)和二环氧丁烷(DEB)对B6C3F1小鼠脾T细胞的诱变潜能和致突变谱。吸入625 ppm的小白鼠。治疗2周的BD患者HPRT(-)突变频率平均为6.2×10(-6)，而对照组为1.2×10(-6)。小鼠每天三次ip。剂量分别为60、80和100NAG EB/kg或7、14和21 mg DEB/kg。EB组HPRT(-)频率分别为5.4×10~(-6)、4.1×10~(-6)和8.6×10~(-6)，DEB组分别为4.6×10~(-6)、9.4×10~(-6)和13×10~(-6)。DNA测序显示，BD、EB和DEB在体内诱导的突变中约有一半是移码突变。这三个化合物在外显子3的6个连续的鸟嘌呤碱基上都观察到了+1移码的‘热点’。BD、EB和DEB产生的其余突变均为AT和GC碱基对的转换和颠换突变。BD引起的碱基对替换偏向于AT碱基对的突变。BD、EB和DEB产生的突变光谱与以前观察到的环氧乙烷的突变光谱非常相似，表明这些环氧化剂可能通过类似的诱变机制发挥作用。
The mutagenic potential and mutational spectra of butadiene (BD), 1,2-epoxybutene (EB), and diepoxybutane (DEB) were determined in splenic T cells from exposed B6C3F1 mice. Mice exposed by inhalation to 625 p.p.m. BD for 2 weeks displayed an average hprt(-) mutation frequency of 6.2 x 10(-6) compared to 1.2x10(-6) in controls. Mice were also given three daily i.p. doses of 60, 80 and 100 nag EB/kg or 7, 14 and 21 mg DEB/kg. Average hprt(-) frequencies of 5.4 x 10(-6) 4.1x10(-6) and 8.6x10(-6) were seen in the EB groups, respectively, while average frequencies of 4.6x10(-6) 9.4x10(-6) and 13x10(-6) were seen in the DEB groups. DNA sequencing revealed that approximately half of the mutations induced in vivo by BD, EB and DEB were frameshift mutations. A +1 frameshift 'hotspot' in six consecutive guanine bases in exon 3 was observed with all three compounds. The remaining mutations produced by BD, EB and DEB were transition and transversion mutations at both AT and GC base pairs. Base pair substitutions induced by BD were biased in favor of mutation at AT base pairs. The mutational spectra produced by BD, EB and DEB were very similar to that observed previously with ethylene oxide, suggesting that these epoxide agents may be working through a similiar mutagenic mechanism.