Molecular study on the urothelial tumor occurrel in dye workers exposed to aromatic amines

第二次世界大战后，和歌山市的许多工厂大量生产芳香胺中间体，作为生产染料的原料。这些工厂的员工中尿路上皮癌的发病率很高。我科一直在对这些患者进行流行病学研究，并报道了这些癌症与一般人群中尿路上皮癌的生物学行为差异。然而，病理组织学研究并没有显示职业性尿路上皮癌的生物学行为与普通人群的生物学行为有明显差异。这些研究的目的是利用分子生物学技术发现这些差异。染工接触芳香胺致癌物代谢酶谷胱甘肽s -转移酶M1 （GSTM1）的遗传研究：我们利用PCR方法研究了GSTM1基因缺失作为宿主特异性因子的可能性，发现与一般人群相比，染工中这种基因缺失的发生率有增加的趋势。对职业环境因素与GSTM1基因缺失患者关系的研究表明，在小型工厂工作且工作时间较长的患者患尿路上皮癌的频率高于在大型工厂工作时间较短的患者。我们将继续对另一种特定的致癌物代谢酶n-乙酰转移酶进行类似的研究。职业性尿路上皮癌中p53基因突变的研究：已有报道尿路上皮癌患者中p53肿瘤抑制基因突变。为了发现职业性尿路上皮癌和自然发生的尿路上皮癌之间的差异，我们一直在准备开展一项研究项目，研究职业性尿路上皮癌患者中p53基因突变形式的可能过表达。然而，我们无法在拟议的研究期结束前完成这个项目。少

Immediately after World War II,many factories in Wakayama City manufactured large quantities of aromatic amine intermediates as raw materials for the production of dyes. These has been a high incidence of urothelial cancers among the employees of these factories. Our Department has been conducting epidemiological studies on these patients and reported the differences in biological behaviors of these cancers and urothelial cancers in the general population. Pathohistological studies, however, have not shown distinct differences between biological behaviors of occupational urothelial cancers and those found in the general population. These studies were conducted with the goal of finding such differences using molecular biology techniques.1. Genetic studies of carcinogen-metabolism enzyme, glutathione S-transferase M1 (GSTM1) in dye workers exposed to aromatic amines : We investigated the possible gene deficiency of GSTM1 as a host-specific factor using the PCR method and found a tendency … More toward an increased incidence of such gene deficiency among dye workers compared with those patients in the general population. Studies on the relationship between occupational environmental factors and the patients with GSTM1 gene deficiency showed that the frequency of urothelial cancers among patients who worked in smaller factories and who worked longer periods of time were higher than among those who worked in larger factories and for shorter periods of time. We will continue to do similar studies on another specific carcinogen-metabolism enzyme, N-acetyltransferase.2. Studies on the mutation of p53 gene in occupatoinal urothelial cancers : Mutation of the p53 tumor suppresser gene in patients with urothelial cancers has been reported. In an attempt to find differences between occupational and naturally-occurring urothelial cancers, we have been preparing to conduct a research project to study the possible overexpression of the mutant forms of the p53 gene in patients with occupational urothelial cancers. We, however, were unable to complete this projsct by the end of the proposed research period. Less