Pan G, Hanaoka T, Yamano Y, Hara K, Ichiba M, Wang Y, Zhang J, Feng Y, Shujuan Z, Guan D, Gao G, Liu N, Takahashi K
Liaoning Public Health and Anti-epidemic Station Heping District, Shenyang, People's Republic of China.
Carcinogenesis. 1998 Nov;19(11):1963-8. doi: 10.1093/carcin/19.11.1963.
We conducted a cross-sectional molecular epidemiological study of coke oven workers exposed to the established carcinogen polycyclic aromatic hydrocarbons (PAHs) to evaluate the relationships between both traditional 'exposure markers' and a series of biomarkers, including urinary 1-hydroxypyrene as a marker of internal dose, leukocyte aromatic DNA adducts as markers of biologically effective dose, serum p53 protein as a response marker and genetic polymorphisms of cytochrome P4501A1 and glutathione S-transferase MI as susceptibility markers. Twenty-five male subjects each were randomly selected from the top, middle and bottom work areas of the oven, and the control plant. They were matched for age and smoking status. The mean levels of PAH exposure, monitored by stationary and personal samplers, and of worker urinary 1-hydroxypyrene differed significantly between the top, middle and bottom of the oven and control work areas. The highest stationary and personal PAH concentrations and 1-hydroxypyrene levels were demonstrated at the top work area. Good correlations were found between the stationary PAH levels, personal PAH levels and urinary 1-hydroxypyrene levels. No positive correlations were demonstrated between aromatic DNA adduct levels and current or cumulative PAH exposure dose. In the presence of genetic polymorphisms of cytochrome P4501A1, a positive correlation was demonstrated between aromatic DNA adducts and urinary 1-hydroxypyrene levels. There was also a significant correlation between serum p53 protein levels and the cumulated benzo[a]pyrene exposure dose. Although these biomarkers have certain limitations, they are applicable to cancer epidemiology, and may contribute to our understanding of the mechanisms of carcinogenesis.
我们对接触已确定致癌物多环芳烃(PAHs)的焦炉工人进行了一项横断面分子流行病学研究,以评估传统“接触标志物”与一系列生物标志物之间的关系,这些生物标志物包括作为内剂量标志物的尿1-羟基芘、作为生物有效剂量标志物的白细胞芳香族DNA加合物、作为反应标志物的血清p53蛋白以及作为易感性标志物的细胞色素P4501A1和谷胱甘肽S-转移酶MI的基因多态性。从焦炉的顶部、中部和底部工作区域以及对照工厂中各随机选取25名男性受试者。他们在年龄和吸烟状况方面进行了匹配。通过固定和个人采样器监测的PAH接触平均水平以及工人尿1-羟基芘水平在焦炉的顶部、中部和底部与对照工作区域之间存在显著差异。在顶部工作区域显示出最高的固定和个人PAH浓度以及1-羟基芘水平。固定PAH水平、个人PAH水平和尿1-羟基芘水平之间发现了良好的相关性。芳香族DNA加合物水平与当前或累积PAH接触剂量之间未显示出正相关。在存在细胞色素P4501A1基因多态性的情况下,芳香族DNA加合物与尿1-羟基芘水平之间显示出正相关。血清p53蛋白水平与累积苯并[a]芘接触剂量之间也存在显著相关性。尽管这些生物标志物有一定局限性,但它们适用于癌症流行病学,可能有助于我们理解致癌机制。