Carstensen U, Alexandrie A K, Högstedt B, Rannug A, Bratt I, Hagmar L
Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden.
Mutat Res. 1993 Oct;289(2):187-95. doi: 10.1016/0027-5107(93)90069-r.
Epidemiological studies have shown an increased incidence of lung cancer, bladder cancer, and esophageal cancer in chimney sweeps, probably due to their exposure to PAH in soot. The work environment for sweeps has, however, improved during the last decades. It was thus important to assess whether the present exposure still may cause genotoxic effects. A further objective was to assess whether genetic polymorphisms in metabolic enzyme activities could explain some of the variation in the parameters of genotoxicity. Venous blood samples were drawn from 71 chimney sweeps and 59 control subjects. Micronuclei were analyzed in activated peripheral B- and T-lymphocytes with preserved cytoplasm. Polymorphisms for CYP1A1 and GST1 in the sweeps were analyzed by a PCR technique. The sweeps did not have higher frequencies of micronuclei in B- or T-lymphocytes than the control subjects, when allowance was made for age and smoking in a multiple regression analysis. Further, there was no association between years of active work as a sweep and any of the two micronucleus parameters. None of the sweeps had the rare CYP1A1 genotype val/val and only one individual had the m2/m2 genotype. The presence of at least one GST1 allele (GST1+) was observed in 36 subjects (51.4%). Thirteen individuals (18.6%) were of the m1/m2 or m2/m2 genotype. And among those only seven had the combined GST1- and m1/m2 genotype. No difference was observed in B- or T-lymphocyte micronucleus frequencies between sweeps with the rare CYP1A1 genotypes m1/m2, m2/m2 or ile/val compared to individuals with the m1/m1 and ile/ile genotypes. Moreover, the GST1 deficient sweeps (GST1-) did not show any altered micronucleus frequency compared to the GST1 positive sweeps. A possible reason for the lack of genotoxic effect in sweeps is the improved hygienic conditions and change in fuels, which has decreased the exposure levels for PAH. Host polymorphisms for metabolizing enzymes did not influence the micronucleus frequencies. As the sweeps did not differ from the control subjects, with respect to micronucleus frequencies, no conclusion on the importance of host polymorphisms for genotoxic risk can be drawn.
流行病学研究表明，烟囱清洁工患肺癌、膀胱癌和食道癌的发病率有所增加，这可能是由于他们接触煤烟中的多环芳烃所致。然而，在过去几十年里，清洁工的工作环境有所改善。因此，评估目前的接触是否仍可能导致遗传毒性效应非常重要。另一个目标是评估代谢酶活性的基因多态性是否可以解释遗传毒性参数的一些变化。从71名烟囱清洁工和59名对照受试者中采集静脉血样。在保留细胞质的活化外周B淋巴细胞和T淋巴细胞中分析微核。通过PCR技术分析清洁工中CYP1A1和GST1的多态性。在多元回归分析中考虑年龄和吸烟因素后，烟囱清洁工的B淋巴细胞或T淋巴细胞中的微核频率并不高于对照受试者。此外，作为清洁工的工作年限与两个微核参数中的任何一个均无关联。没有一个烟囱清洁工具有罕见的CYP1A1基因型val/val，只有一个个体具有m2/m2基因型。在36名受试者（51.4%）中观察到至少一个GST1等位基因（GST1+）的存在。13名个体（18.6%）为m1/m2或m2/m2基因型。在这些人中，只有7人具有GST1-和m1/m2的联合基因型。与具有m1/m1和ile/ile基因型的个体相比，具有罕见CYP1A1基因型m1/m2、m2/m2或ile/val的烟囱清洁工的B淋巴细胞或T淋巴细胞微核频率没有差异。此外，与GST1阳性的烟囱清洁工相比，GST1缺陷的烟囱清洁工（GST1-）的微核频率没有任何改变。烟囱清洁工缺乏遗传毒性效应的一个可能原因是卫生条件的改善和燃料的变化，这降低了多环芳烃的接触水平。代谢酶的宿主多态性并未影响微核频率。由于烟囱清洁工在微核频率方面与对照受试者没有差异，因此无法得出关于宿主多态性对遗传毒性风险重要性的结论。
