Holz O, Krause T, Rüdiger H W
Department of Occupational Medicine, University of Hamburg, FRG.
Carcinogenesis. 1991 Nov;12(11):2181-3. doi: 10.1093/carcin/12.11.2181.
It was the aim of this study to compare the formation of DNA adducts in different human white blood cells. Lymphocytes and monocytes were isolated from peripheral blood by density centrifugation and by a monocyte-specific antibody linked to magnetic beads. DNA adducts were determined by 32P-postlabelling. After in vitro incubation with benzo[a]-pyrene (B[a]P) we found DNA adducts in monocytes, but not in unstimulated blood lymphocytes. Only after growth stimulation by phytohaemagglutinin did lymphocytes show an adduct pattern similar to monocytes. In contrast, B[a]P-7,8-dihydro-9,10-diolepoxide, an activated intermediate of B[a]P metabolism leads to similar DNA adducts in both cell types. When lymphocytes were incubated in the presence of B[a]P together with monocytes, then after subsequent separation lymphocytes exhibited most of the adducts found in monocytes, though to a lower extent. Our results suggest that unstimulated blood lymphocytes--which are unable to activate metabolically promutagens like B[a]P--receive the genotoxic material to form DNA adducts from other blood cells or from cells in the vessel lining. We conclude that the amount and the pattern of DNA adducts formed in whole white blood cells may be influenced considerably by a variable proportion of monocytes.
本研究的目的是比较不同人类白细胞中DNA加合物的形成情况。通过密度离心和与磁珠相连的单核细胞特异性抗体从外周血中分离淋巴细胞和单核细胞。采用³²P后标记法测定DNA加合物。在与苯并[a]芘（B[a]P）进行体外孵育后，我们在单核细胞中发现了DNA加合物，但在未受刺激的血液淋巴细胞中未发现。只有在植物血凝素刺激生长后，淋巴细胞才显示出与单核细胞相似的加合物模式。相比之下，B[a]P代谢的活性中间体B[a]P - 7,8 - 二氢 - 9,10 - 二环氧物在两种细胞类型中导致相似的DNA加合物。当淋巴细胞与单核细胞一起在B[a]P存在的情况下孵育，随后分离后，淋巴细胞显示出在单核细胞中发现的大部分加合物，尽管程度较低。我们的结果表明，未受刺激的血液淋巴细胞——无法代谢激活像B[a]P这样的前诱变剂——从其他血细胞或血管内皮细胞接收遗传毒性物质以形成DNA加合物。我们得出结论，全白细胞中形成的DNA加合物的数量和模式可能会受到单核细胞可变比例的显著影响。
