Arce G T, Vincent D R, Cunningham M J, Choy W N, Sarrif A M
Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours & Company, Inc., Newark, DE 19714.
Environ Health Perspect. 1990 Jun;86:75-8. doi: 10.1289/ehp.908675.
1,3-Butadiene and two major genotoxic metabolites 3,4-epoxybutene (EB) and 1,2:3,4-diepoxybutane (DEB) were used as model compounds to determine if genetic toxicity findings in animal and human cells can aid in extrapolating animal toxicity data to man. Sister chromatid exchange (SCE) and micronucleus induction results indicated 1,3-butadiene was genotoxic in the bone marrow of the mouse but not the rat. This paralleled the chronic bioassays which showed mice to be more susceptible than rats to 1,3-butadiene carcinogenicity. However, 1,3-butadiene did not induce unscheduled DNA synthesis (UDS) in the rat or mouse hepatocytes following in vivo exposure. Likewise, UDS in rat and mouse hepatocytes in vitro was not induced by EB or DEB. Salmonella typhimurium gene mutation (Ames) tests of 1,3-butadiene using strains TA1535, TA97, TA98, and TA100 and employing rat, mouse, and human liver S9 metabolic systems were barely 2-fold above background only in strain TA1535 at 30% 1,3-butadiene in air with induced and uninduced rat S9 and mouse S9 (uninduced). 1,3-Butadiene was negative in in vitro SCE studies in human whole blood lymphocytes cultures treated in the presence of rat, mouse, or human liver S9 metabolic activation. In general, 1,3-butadiene is genotoxic in vivo but is a weak in vitro genotoxin.
1,3 - 丁二烯以及两种主要的基因毒性代谢物3,4 - 环氧丁烯（EB）和1,2:3,4 - 二环氧丁烷（DEB）被用作模型化合物，以确定动物和人类细胞中的遗传毒性研究结果是否有助于将动物毒性数据外推至人类。姐妹染色单体交换（SCE）和微核诱导结果表明，1,3 - 丁二烯对小鼠骨髓具有遗传毒性，但对大鼠骨髓无遗传毒性。这与慢性生物测定结果一致，慢性生物测定表明小鼠比大鼠对1,3 - 丁二烯致癌性更敏感。然而，体内暴露后，1,3 - 丁二烯未在大鼠或小鼠肝细胞中诱导非程序性DNA合成（UDS）。同样，EB或DEB也未在体外诱导大鼠和小鼠肝细胞中的UDS。使用TA1535、TA97、TA98和TA100菌株以及大鼠、小鼠和人肝脏S9代谢系统对1,3 - 丁二烯进行的鼠伤寒沙门氏菌基因突变（Ames）试验，仅在含30% 1,3 - 丁二烯的空气中，使用诱导和未诱导的大鼠S9以及未诱导的小鼠S9时，在TA1535菌株中比背景值仅高出2倍左右。在存在大鼠、小鼠或人肝脏S9代谢激活的情况下处理的人全血淋巴细胞培养物的体外SCE研究中，1,3 - 丁二烯呈阴性。总体而言，1,3 - 丁二烯在体内具有遗传毒性，但在体外是一种弱遗传毒素。
