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

第二次世界大战结束后，和歌山市的许多工厂立即生产了大量芳香胺中间体，作为生产染料的原料。在这些工厂的员工中，尿路上皮癌的发病率一直很高。我科一直在对这些患者进行流行病学研究，并报告了这些癌症和尿路上皮癌在普通人群中的生物学行为差异。然而，病理组织学研究并未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种差异。染料工人致癌物代谢酶谷胱甘肽S转移酶M1的遗传学研究：我们用聚合酶链式反应的方法研究了作为宿主特异性因子的谷胱甘肽S转移酶M1可能的基因缺陷，发现有…的倾向与普通人群中的患者相比，染料工人中此类基因缺陷的发生率更高。对职业环境因素与GSTM1基因缺陷患者关系的研究表明，在较小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较大工厂工作且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。尿路上皮癌中P53基因突变的研究：已有报道P53抑癌基因在尿路上皮癌中的突变。为了找出职业性尿路上皮癌和自然发生的尿路上皮癌之间的差异，我们一直在准备进行一项研究项目，以研究职业性尿路上皮癌患者中可能存在的p53基因突变形式的过度表达。然而，我们未能在拟议的研究期结束前完成这一项目。较少

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