Ichiba M, Hagmar L, Rannug A, Högstedt B, Alexandrie A K, Carstensen U, Hemminki K
Unit of Molecular Epidemiology, Karolinska Institute, Huddinge, Sweden.
Carcinogenesis. 1994 Jul;15(7):1347-52. doi: 10.1093/carcin/15.7.1347.
Aromatic DNA adducts in total white blood cells, cytochrome P450 (CYP) class 1A1 and glutathione transferase (GST1) class mu genotypes and micronuclei in T- and B-lymphocytes were studied in 69 full-time chimney sweeps and 35 controls, all male subjects. The sweeps had a higher (22%) but statistically non-significant increase in the level of DNA adducts as compared to the controls when all individuals independent of genotype were compared. The non-inducible CYP1A1 genotype, m1/m1, lacking a MspI restriction site at the 3' end of the gene, was associated with significantly higher adduct levels in the sweeps. Among the 26 sweeps with the combined genotype m1/m1 and GST1(-), a statistically significant 60% increase in median adduct levels was observed as compared with those 14 control subjects with the corresponding genotype. Smoking also showed a significant effect on the level of adducts. The effect on DNA adducts by sweeping, smoking and genotype appeared to be additive and independent of each other. DNA adducts in sweeps were moderately but statistically significantly correlated with micronuclei in both T- and B-lymphocytes. The correlation between adduct levels and micronuclei was most marked in T-lymphocytes of individuals lacking the GST1 gene.
对69名全职烟囱清洁工和35名对照者（均为男性）的全血白细胞中的芳香族DNA加合物、细胞色素P450（CYP）1A1类和谷胱甘肽S-转移酶（GST1）μ类基因型以及T淋巴细胞和B淋巴细胞中的微核进行了研究。当比较所有不考虑基因型的个体时，与对照组相比，烟囱清洁工的DNA加合物水平有较高（22%）但无统计学意义的升高。基因3'端缺乏MspI限制性位点的非诱导型CYP1A1基因型m1/m1，与烟囱清洁工中显著更高的加合物水平相关。在26名具有m1/m1和GST1（-）组合基因型的烟囱清洁工中，与14名具有相应基因型的对照者相比，观察到加合物水平中位数有统计学意义的60%的升高。吸烟对加合物水平也有显著影响。清扫、吸烟和基因型对DNA加合物的影响似乎是相加的且相互独立。烟囱清洁工中的DNA加合物与T淋巴细胞和B淋巴细胞中的微核呈中度但有统计学意义的相关性。在缺乏GST1基因的个体的T淋巴细胞中，加合物水平与微核之间的相关性最为明显。
