Perera F P, Hemminki K, Young T L, Brenner D, Kelly G, Santella R M
Division of Environmental Sciences, Columbia University School of Public Health, New York, New York 10032.
Cancer Res. 1988 Apr 15;48(8):2288-91.
Iron foundry workers, exposed to high levels of polycyclic aromatic hydrocarbons (PAHs), silica, and metal fumes and dusts, are at elevated risk of lung cancer. Benzo(a)pyrene and a number of structurally related PAHs are metabolically activated to diol epoxides (e.g., 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a) pyrene) which are mutagenic, carcinogenic in experimental animals, and form covalent adducts with DNA. The levels of these adducts were measured in an enzyme-linked immunosorbent assay using a polyclonal anti-benzo(a)pyrene diol epoxide-I-DNA antibody which cross-reacts with DNA modified by diol epoxides of structurally related PAHs. DNA was analyzed from peripheral blood cells of 35 Finnish foundry workers and 10 controls. Workers were classified as having low (less than 0.05 micrograms/m3), medium (0.05-0.2 micrograms/m3), or high (greater than 0.2 micrograms/m3) exposure to benzo(a)pyrene (as an indicator of PAH). When adjustment was made for cigarette smoking and time since vacation, benzo(a)pyrene exposure was significantly related to adduct levels (P = 0.0001). Each of the three exposure groups had significantly elevated adduct levels compared to controls. Among the exposed workers, the low group differed significantly from the high and medium categories. This study supports the usefulness of monitoring adduct formation in a population occupationally exposed to carcinogens.
铸铁工人接触高浓度的多环芳烃(PAHs)、二氧化硅以及金属烟雾和粉尘,患肺癌的风险较高。苯并(a)芘和一些结构相关的多环芳烃经代谢激活生成二醇环氧化物(例如,7β,8α-二羟基-9α,10α-环氧-7,8,9,10-四氢苯并(a)芘),这些二醇环氧化物具有致突变性,在实验动物中具有致癌性,并能与DNA形成共价加合物。使用一种多克隆抗苯并(a)芘二醇环氧化物-I-DNA抗体,通过酶联免疫吸附测定法测量这些加合物的水平,该抗体与由结构相关的多环芳烃二醇环氧化物修饰的DNA发生交叉反应。对35名芬兰铸造工人和10名对照者的外周血细胞进行了DNA分析。根据工人接触苯并(a)芘(作为多环芳烃的指标)的水平分为低(低于0.05微克/立方米)、中(0.05 - 0.2微克/立方米)、高(高于0.2微克/立方米)暴露组。在对吸烟情况和自休假以来的时间进行调整后,苯并(a)芘暴露与加合物水平显著相关(P = 0.0001)。与对照组相比,三个暴露组的加合物水平均显著升高。在暴露工人中,低暴露组与高暴露组和中暴露组有显著差异。本研究支持在职业接触致癌物的人群中监测加合物形成的实用性。