Ong T, Nath J
Division of Plant and Soil Sciences, College of Agriculture and Forestry, West Virginia University, Morgantown 26506-6108.
Environ Mol Mutagen. 1992;20(2):117-26. doi: 10.1002/em.2850200207.
Micronuclei kinetics and persistence in mononucleated and binucleated human peripheral lymphocytes following short-term (4 hr) and continuous (until harvest) in vitro exposure to vincristine sulfate (VS) and ethylene dibromide (EDB) were studied. Lymphocytes were exposed to chemicals for various doses and harvested at different culture times. Micronucleus frequencies were scored in both mononucleated and binucleated cells on the same slide. VS-treated cells showed a significantly higher incidence of micronucleus in both mononucleated and binucleated cells than controls (P less than 0.01). The cells treated continuously with VS produced comparatively higher frequencies of micronucleated cells than those treated for 4 hr. Highest micronuclei frequencies were observed 24 hr after chemical treatment in both mononucleated and binucleated cells and decreased later with time. However, the micronucleus frequencies remained significantly higher than the controls even in the cells harvested at 144 hr. VS induced a large number of micronucleated cells with multiple micronuclei. VS also caused a severe decrease in nuclear division due to cytotoxic effect. Lymphocytes treated with EDB for 4 hr and continuously showed a statistically higher incidence of micronuclei in binucleated cells compared to the controls (P less than 0.05), whereas in mononucleated cells higher micronucleus frequencies were observed only in cultures treated continuously. Continuous presence of EDB induced both dose- and time-dependent increase of micronuclei in both mono- and binucleated cells (P less than 0.05). EDB induced relatively few multiple micronucleated cells in comparison with VS. EDB did not affect nuclear divisions even with continuous treatment. High micronucleus frequencies observed at 144 hr harvest following 4 hr treatment of both EDB and VS suggest the persistence of DNA damage in cells. These studies suggest that micronuclei kinetics in human peripheral lymphocytes depends on the genotoxic potentially and cytotoxicity of a genotoxicant.
研究了人外周血单核细胞和双核细胞在短期（4小时）和持续（直至收获）体外暴露于硫酸长春新碱（VS）和1,2-二溴乙烷（EDB）后微核的动力学和持续性。淋巴细胞暴露于不同剂量的化学物质，并在不同培养时间收获。在同一张载玻片上对单核细胞和双核细胞中的微核频率进行评分。与对照组相比，VS处理的单核细胞和双核细胞中微核发生率均显著更高（P<0.01）。持续用VS处理的细胞产生的微核化细胞频率比处理4小时的细胞更高。在化学处理后24小时，单核细胞和双核细胞中均观察到最高的微核频率，随后随时间下降。然而，即使在144小时收获的细胞中，微核频率仍显著高于对照组。VS诱导了大量具有多个微核的微核化细胞。VS还由于细胞毒性作用导致核分裂严重减少。与对照组相比，EDB处理4小时和持续处理的双核细胞中微核发生率在统计学上显著更高（P<0.05），而在单核细胞中，仅在持续处理的培养物中观察到更高的微核频率。EDB的持续存在导致单核细胞和双核细胞中微核的剂量和时间依赖性增加（P<0.05）。与VS相比，EDB诱导的具有多个微核的细胞相对较少。即使持续处理，EDB也不影响核分裂。在EDB和VS处理4小时后144小时收获时观察到的高微核频率表明细胞中DNA损伤的持续性。这些研究表明，人外周血淋巴细胞中的微核动力学取决于遗传毒性物质的遗传毒性潜力和细胞毒性。
