Cochrane J E, Skopek T R
Department of Pathology, University of North Carolina at Chapel Hill 27599-7525.
Carcinogenesis. 1994 Apr;15(4):719-23. doi: 10.1093/carcin/15.4.719.
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 1.2 x 10(-6) in controls. Mice were also given three daily i.p. doses of 60, 80 and 100 mg EB/kg or 7, 14 and 21 mg DEB/kg. Average hprt- frequencies of 5.4 x 10(-6), 4.1 x 10(-6) and 8.6 x 10(-6) were seen in the EB groups, respectively, while average frequencies of 4.6 x 10(-6), 9.4 x 10(-6) and 13 x 10(-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 similar mutagenic mechanism.
测定了暴露于丁二烯（BD）、1,2 - 环氧丁烯（EB）和1,2 - 二环氧丁烷（DEB）的B6C3F1小鼠脾T细胞中的诱变潜力和突变谱。通过吸入625 ppm BD暴露2周的小鼠，其平均次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（hprt）突变频率为6.2×10⁻⁶，而对照组为1.2×10⁻⁶。小鼠还每天经腹腔注射给予60、80和100 mg EB/kg或7、14和21 mg DEB/kg。在EB组中分别观察到平均hprt频率为5.4×10⁻⁶、4.1×10⁻⁶和8.6×10⁻⁶，而在DEB组中分别观察到平均频率为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一半是移码突变。在所有三种化合物中均观察到外显子3中六个连续鸟嘌呤碱基处的 +1移码“热点”。BD、EB和DEB产生的其余突变是AT和GC碱基对处的转换和颠换突变。BD诱导的碱基对替换倾向于在AT碱基对处发生突变。BD、EB和DEB产生的突变谱与先前观察到的环氧乙烷非常相似，表明这些环氧化合物可能通过类似的诱变机制起作用。
