Srám R J, Binková B
Laboratory of Genetic Ecotoxicology, Regional Institute of Hygiene of Central Bohemia and Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Environ Health Perspect. 2000 Mar;108 Suppl 1(Suppl 1):57-70. doi: 10.1289/ehp.108-1637778.
Molecular epidemiology is a new and evolving area of research, combining laboratory measurement of internal dose, biologically effective dose, biologic effects, and influence of individual susceptibility with epidemiologic methodologies. Biomarkers evaluated were selected according to basic scheme: biomarkers of exposure--metabolites in urine, DNA adducts, protein adducts, and Comet assay parameters; biomarkers of effect--chromosomal aberrations, sister chromatid exchanges, micronuclei, mutations in the hypoxanthine-guanine phosphoribosyltransferase gene, and the activation of oncogenes coding for p53 or p21 proteins as measured on protein levels; biomarkers of susceptibility--genetic polymorphisms of genes CYP1A1, GSTM1, GSTT1, NAT2. DNA adducts measured by 32P-postlabeling are the biomarker of choice for the evaluation of exposure to polycyclic aromatic hydrocarbons. Protein adducts are useful as a biomarker for exposure to tobacco smoke (4-aminobiphenyl) or to smaller molecules such as acrylonitrile or 1,3-butadiene. Of the biomarkers of effect, the most common are cytogenetic end points. Epidemiologic studies support the use of chromosomal breakage as a relevant biomarker of cancer risk. The use of the Comet assay and methods analyzing oxidative DNA damage needs reliable validation for human biomonitoring. Until now there have not been sufficient data to interpret the relationship between genotypes, biomarkers of exposure, and biomarkers of effect for assessing the risk of human exposure to mutagens and carcinogens.
分子流行病学是一个新兴且不断发展的研究领域，它将内部剂量、生物有效剂量、生物效应的实验室测量以及个体易感性的影响与流行病学方法相结合。所评估的生物标志物是根据基本方案选择的：暴露生物标志物——尿液中的代谢物、DNA加合物、蛋白质加合物和彗星试验参数；效应生物标志物——染色体畸变、姐妹染色单体交换、微核、次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶基因中的突变，以及在蛋白质水平上测量的编码p53或p21蛋白的癌基因激活；易感性生物标志物——CYP1A1、GSTM1、GSTT1、NAT2基因的遗传多态性。通过32P后标记法测量的DNA加合物是评估多环芳烃暴露的首选生物标志物。蛋白质加合物可用作接触烟草烟雾（4-氨基联苯）或丙烯腈或1,3-丁二烯等小分子的生物标志物。在效应生物标志物中，最常见的是细胞遗传学终点。流行病学研究支持将染色体断裂用作癌症风险的相关生物标志物。彗星试验和分析氧化性DNA损伤的方法在用于人体生物监测时需要可靠的验证。到目前为止，还没有足够的数据来解释基因型、暴露生物标志物和效应生物标志物之间的关系，以评估人类接触诱变剂和致癌物的风险。
