Golka K, Seidel T, Dietrich H, Roth G, Rötzel C, Thier R, Geller F, Reckwitz T, Schulze H
Institut für Arbeitsphysiologie an der Universität Dortmund, Ardeystr. 67, D-44139 Dortmund.
Aktuelle Urol. 2005 Sep;36(5):417-22. doi: 10.1055/s-2004-830260.
Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e. g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1 - 2 carbon atoms) were investigated.
At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR.
Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6 %) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8 %) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative).
The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis.
几种职业致癌物由多态性酶代谢。研究了多态性酶N - 乙酰转移酶2(NAT2;底物:芳香胺)、谷胱甘肽S - 转移酶M1(GSTM1;底物:例如多环芳烃的活性代谢物)和谷胱甘肽S - 转移酶T1(GSTT1;底物:含1 - 2个碳原子的小分子)的分布情况。
在维滕贝格市路德施塔特的泌尿外科,对136例经组织学证实为膀胱移行细胞癌的患者进行了调查,了解他们从事超过6个月的所有职业。询问了几种职业和非职业风险因素。通过聚合酶链反应从白细胞DNA中确定NAT2、GSTM1和GSTT1的基因型。
与中欧普通人群相比,GSTT1阴性者的比例(22.1%)正常;慢乙酰化者的比例(59.6%)处于正常范围上限,而GSTM1阴性者在整个组中的比例(58.8%)升高。在接触石棉(6/6 GSTM1阴性,5/6慢乙酰化者)、橡胶制造(8/10 GSTM1阴性)和氯化溶剂(9/15 GSTM1阴性)的亚组中观察到基因型分布的变化。
在这个工业化地区GSTM1阴性膀胱癌患者的比例过高,并且在几个职业暴露亚组中更为明显,这表明GSTM1阴性基因型在膀胱癌发生过程中有影响。