1998年,发行了名为“民事诉讼”的变形虫。电影描述了沃本的案子,始于1982年,于1990年结束,这是三氯乙烯污染最著名的案例之一。在波士顿附近的一个小镇,十二个孩子死于白血病,这似乎归因于饮用水中的三氯乙烯污染。受害者,然而,无法赢得这场官司,因为确定的化学物质可能导致白血病和其他人类疾病的证据相当粗略。在包括日本在内的工业国家中,有许多三氯乙烯污染的案例,因此,我们重新考虑了缺失的环节。我们的结论是,该疾病的发生不是由于化学危害对生物大分子的直接影响,而是通过信号转导和转录调节等生理系统的间接影响。1984年,我们报道了三氯乙烯暴露导致的调节血红素池显著减少,然而,生物学意义还没有得到很好的理解。最近,我们发现基因的负调节因子Bach1的DNA结合活性,由血红素控制,这种调节似乎解释了白血病是如何发展的。具有MafK的Bach1的异二聚体识别Maf识别元件(MARE)与红系型正调节因子竞争,NF-E2与MafK的复合物。Bach1/MafK在低血红素条件下占据马雷斯,而随着血红素浓度的增加,MARE对NF-E2/MafK开放。由于NF-E2/MafK功能与正常红系分化密切相关,其中铁粒幼细胞性贫血等疾病通常与瘤形成有关;即,一种可以发展为白血病的克隆疾病。因此,三氯乙烯中毒引起的调节性血红素的显著下降可能是导致白血病的途径之一。
In 1998, a amovie entitled \"A Civil Action\" was released. The movie described the Woburn
case, begun in 1982 and concluded in 1990, one of the most famous cases of trichloroethylene pollution. In a small town near Boston, twelve children died of leukemia, which seemed attributable to trichloroethylene contamination of the drinking water. The victims, however, could not win the
case, since evidence that the identified chemicals could cause leukemia and other human illnesses was rather sketchy. There have been many cases of trichloroethylene pollution in industrial nations including Japan, therefore, we reconsidered the missing link. Our conclusion is that the disease occurred not by a direct effect of the chemical hazard on biological macromolecules but by an indirect effect through the physiological system such as signal transduction and transcriptional regulation. In 1984, we reported a marked reduction in the regulatory heme pool by trichloroethylene exposure, however, the biological significance was not well understood. Recently, we found that the DNA binding activity of
Bach1, a negative regulator of genes, is controlled by heme, the regulation of which seems to explain how leukemia develops. The heterodimer of
Bach1 with MafK recognizes Maf recognition elements (MAREs) competing with the erythroid type positive regulator, a complex of NF-E2 with MafK.
Bach1/MafK occupies MAREs under lower heme conditions, whereas MAREs are open to NF-E2/MafK along with increasing heme concentration. Since the NF-E2/MafK function is closely related to normal erythroid differentiation, of which disorders such as sideroblastic anemia are often related to neoplasia; i.e., a clonal disorder that can progress to leukemia. Thus, a marked decline in regulatory heme by trichloroethylene intoxication could be one of the pathways to leukemia.