Srám R J
Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine and Regional Institute of Hygiene of Central Bohemia, Prague, Czech Republic.
Environ Health Perspect. 1998 Feb;106 Suppl 1(Suppl 1):231-9. doi: 10.1289/ehp.106-1533289.
Genotypes responsible for interindividual differences in ability to activate or detoxify genotoxic agents are recognized as biomarkers of susceptibility. Among the most studied genotypes are human glutathione transferases. The relationship of genetic susceptibility to biomarkers of exposure and effects was studied especially in relation to the genetic polymorphism of glutathione S-transferase M1 (GSTM1). For this review papers reporting the effect of GSTM1 genotype on DNA adducts, protein adducts, urine mutagenicity, Comet assay parameters, chromosomal aberrations, sister chromatid exchanges (SCE), micronuclei, and hypoxanthine-guanine phosphoribosyl transferase mutations were assessed. Subjects in groups occupationally exposed to polycyclic aromatic hydrocarbons, benzidine, pesticides, and 1,3-butadiene were included. As environmentally exposed populations, autopsy donors, coal tar-treated patients, smokers, nonsmokers, mothers, postal workers, and firefighters were followed. From all biomarkers the effect of GSTM1 and N-acetyl transferase 2 was seen in coke oven workers on mutagenicity of urine and of glutathione S-transferase T1 on the chromosomal aberrations in subjects from 1,3-butadiene monomer production units. Effects of genotypes on DNA adducts were found from lung tissue of autopsy donors and from placentas of mothers living in an air-polluted region. The GSTM1 genotype affected mutagenicity of urine in smokers and subjects from polluted regions, protein adducts in smokers, SCE in smokers and nonsmokers, and Comet assay parameters in postal workers. A review of all studies on GSTM1 polymorphisms suggests that research probably has not reached the stage where results can be interpreted to formulate preventive measures. The relationship between genotypes and biomarkers of exposure and effects may provide an important guide to the risk assessment of human exposure to mutagens and carcinogens.
导致个体在激活或解毒基因毒性剂能力上存在差异的基因型被视为易感性生物标志物。研究最多的基因型之一是人类谷胱甘肽转移酶。尤其针对谷胱甘肽S-转移酶M1（GSTM1）的基因多态性，研究了遗传易感性与暴露生物标志物和效应之间的关系。为撰写本综述，评估了报告GSTM1基因型对DNA加合物、蛋白质加合物、尿液诱变性、彗星试验参数、染色体畸变、姐妹染色单体交换（SCE）、微核以及次黄嘌呤-鸟嘌呤磷酸核糖转移酶突变影响的论文。纳入了职业性接触多环芳烃、联苯胺、农药和1,3-丁二烯的人群。作为环境暴露人群，对尸体解剖供体、接受煤焦油治疗的患者、吸烟者、非吸烟者、母亲、邮政工作人员和消防员进行了跟踪研究。在所有生物标志物中，发现GSTM1和N-乙酰转移酶2对焦炉工人尿液的诱变性有影响，谷胱甘肽S-转移酶T1对来自1,3-丁二烯单体生产单位的受试者的染色体畸变有影响。从尸体解剖供体的肺组织和生活在空气污染地区的母亲的胎盘组织中发现了基因型对DNA加合物的影响。GSTM1基因型影响吸烟者和污染地区受试者尿液的诱变性、吸烟者蛋白质加合物、吸烟者和非吸烟者的SCE以及邮政工作人员的彗星试验参数。对所有关于GSTM1多态性的研究进行综述表明，研究可能尚未达到能够解释结果以制定预防措施的阶段。基因型与暴露生物标志物和效应之间的关系可能为人类接触诱变剂和致癌物的风险评估提供重要指导。
