Pathology Department, College of Medicine, University of Vermont, Burlington, Vermont, USA.
Crit Rev Toxicol. 2010 Oct;40 Suppl 1:12-73. doi: 10.3109/10408444.2010.507182.
1,3-Butadiene’s (BD’s) major electrophilic metabolites 1,2-epoxy-3-butene (EB), 1,2-dihydroxy-3,4-epoxybutane (EBD), and 1,2,3,4-diepoxybutane (DEB) are responsible for both its mutagenicity and carcinogenicity. EB, EBD, and DEB are DNA reactive, forming a variety of adducts. All three metabolites are genotoxic in vitro and in vivo, with relative mutagenic potencies of DEB >> EB > EBD. DEB also effectively produces gene deletions and chromosome aberrations. BD’s greater mutagenicity and carcinogenicity in mice over rats as well as its failure to induce chromosome-level mutations in vivo in rats appear to be due to greater production of DEB in mice. Concentrations of EB and DEB in vivo in humans are even lower than in rats. Although most studies of BD-exposed humans have failed to find increases in gene mutations, one group has reported positive findings. Reasons for these discordant results are examined. BD-related chromosome aberrations have never been demonstrated in humans except for the possible production of micronuclei in lymphocytes of workers exposed to extremely high levels of BD in the workplace. The relative potencies of the BD metabolites, their relative abundance in the different species, and the kinds of mutations they can induce are major considerations in BD’s overall genotoxicity profile.
1,3-丁二烯（BD）的主要亲电代谢物 1,2-环氧-3-丁烯（EB）、1,2-二羟基-3,4-环氧丁烷（EBD）和 1,2,3,4-二环氧丁烷（DEB）是其致突变性和致癌性的主要原因。EB、EBD 和 DEB 具有 DNA 反应性，形成多种加合物。这三种代谢物在体外和体内均具有遗传毒性，DEB 的相对诱变能力>>EB > EBD。DEB 还能有效地产生基因缺失和染色体畸变。BD 在小鼠中的致突变性和致癌性大于大鼠，以及其在大鼠体内未能诱导染色体水平的突变，这似乎是由于在小鼠中产生了更多的 DEB。人体内 EB 和 DEB 的浓度甚至低于大鼠。尽管大多数接触 BD 的人类研究未能发现基因突变增加，但有一组研究报告了阳性结果。这些不一致结果的原因正在被研究。除了在工作场所暴露于极高水平 BD 的工人的淋巴细胞中可能产生微核外，BD 相关的染色体畸变在人类中从未被证明过。BD 代谢物的相对效力、它们在不同物种中的相对丰度以及它们能够诱导的突变类型是 BD 整体遗传毒性特征的主要考虑因素。
