Andersson H C, Kihlman B A
Department of Genetics, Uppsala University, Sweden.
Carcinogenesis. 1989 Jan;10(1):123-30. doi: 10.1093/carcin/10.1.123.
The frequencies of chromosomal aberrations and sister chromatid exchanges (SCE) were studied in human peripheral lymphocytes after exposure of whole blood cultures to the antitumour agent m-AMSA. Chromosome-type aberrations were found in cells exposed before stimulation or during the G1-phase of the cell cycle. Chromatid-type aberrations were obtained in cells exposed during the S- and G2-phases, but also in cells exposed the G1-phase or before stimulation. Treatment of lymphocytes with m-AMSA in the G1-phase or before stimulation had the additional effect of strongly increasing the frequency of SCE. When unstimulated lymphocytes were exposed to m-AMSA, the frequencies of SCE and chromatid-type aberrations, but not the frequency of chromosome-type aberrations, could be strongly reduced by holding the cells in F-10 for 2-4 h before stimulation, or by changing the growth medium after stimulation. A 1-h incubation in growth medium was sufficient for obtaining this reduction. The medium in which the m-AMSA-treated cells were incubated for the first 3 h after stimulation proved to be capable of inducing chromatid-type aberrations in late S/G2-phase and SCEs in the S-phase. These observations show that the chromatid-type aberrations and SCEs obtained by exposing unstimulated lymphocytes to m-AMSA were not produced during the treatment itself, but after stimulation at an advanced stage of the cell cycle by an active substance (m-AMSA or a metabolite of m-AMSA) released into the medium during the first hours of incubation. Post-treatments in G2 with 1-beta-D-arabinofuranosylcytosine (ara-C) and hydroxyurea strongly enhanced the frequency of chromatid-type aberrations obtained after treatment of stimulated or unstimulated lymphocytes with m-AMSA. Post-treatments in unstimulated or G1-phase lymphocytes with ara-C did not influence the frequency of chromosome-type aberrations induced by m-AMSA at these stages, but strongly enhanced those induced by X-rays.
将全血培养物暴露于抗肿瘤药物m-AMSA后，对人外周血淋巴细胞中的染色体畸变频率和姐妹染色单体交换（SCE）进行了研究。在刺激前或细胞周期的G1期暴露的细胞中发现了染色体型畸变。在S期和G2期暴露的细胞中获得了染色单体型畸变，但在G1期或刺激前暴露的细胞中也有发现。在G1期或刺激前用m-AMSA处理淋巴细胞具有强烈增加SCE频率的额外作用。当未刺激的淋巴细胞暴露于m-AMSA时，在刺激前将细胞置于F-10中2-4小时，或在刺激后更换生长培养基，可显著降低SCE和染色单体型畸变的频率，但不能降低染色体型畸变的频率。在生长培养基中孵育1小时就足以实现这种降低。事实证明，在刺激后最初3小时内用于孵育经m-AMSA处理细胞的培养基，能够在S期后期诱导染色单体型畸变，并在S期诱导SCE。这些观察结果表明，通过将未刺激的淋巴细胞暴露于m-AMSA而获得的染色单体型畸变和SCE不是在处理过程中产生的，而是在细胞周期后期刺激时由在孵育最初几小时内释放到培养基中的活性物质（m-AMSA或m-AMSA的代谢产物）产生的。在G2期用1-β-D-阿拉伯呋喃糖基胞嘧啶（ara-C）和羟基脲进行后处理，可强烈提高用m-AMSA处理刺激或未刺激的淋巴细胞后获得的染色单体型畸变频率。在未刺激或G1期淋巴细胞中用ara-C进行后处理，在这些阶段不会影响m-AMSA诱导的染色体型畸变频率，但会强烈提高X射线诱导的畸变频率。
