Pérez-Maldonado Iván N, Díaz-Barriga Fernando, de la Fuente Hortensia, González-Amaro Roberto, Calderón Jaqueline, Yáñez Leticia
Facultad de Medicina, Universidad Autónoma de San Luis Potosí, S.L.P., San Luis Potosí, Mexico.
Environ Res. 2004 Jan;94(1):38-46. doi: 10.1016/s0013-9351(03)00112-9.
The aim of the present work was to investigate whether DDT and its metabolites are able to induce apoptosis of human peripheral blood mononuclear cells (PBMC) both in vitro and in vivo. Cells isolated from healthy individuals were incubated in the presence of increasing concentrations of p'p-DDT, p'p-DDE, or p'p-DDD (0-150 microg/mL) for different intervals. Apoptosis was then determined by flow cytometry (DNA cell content analysis) and fluorescence microscopy (Hoechst staining). A significant level of apoptosis was induced by DDT, DDD, and DDE at 80 microg/mL compared to controls, reaching a maximum effect at 100 microg/mL. We began to detect apoptosis at 12h, with a maximum effect at 24h of incubation. These results were confirmed using the TUNEL assay in cells treated with the three compounds tested as well as with o'p-DDT at 100 microg/mL and 24h of incubation. Our data demonstrate that DDT and its metabolites are able to induce apoptosis of human PBMC in vitro. Therefore, we performed a preliminary study in children exposed to this insecticide. When compared to a control population, the exposed children had higher levels of DDT, DDD, and DDE in blood and also had a higher frequency of apoptosis. In the exposed children, a weak positive association was found between the frequency of apoptosis and the exposure to DDT and DDE. Our results showed that more studies are needed in people exposed to DDT, as apoptosis may cause serious public health effects such as immunosuppression.
本研究的目的是调查滴滴涕(DDT)及其代谢产物是否能够在体外和体内诱导人外周血单个核细胞(PBMC)凋亡。从健康个体分离的细胞在不同时间段内,于浓度不断增加的对,对'-滴滴涕(p'p-DDT)、对,对'-滴滴滴(p'p-DDD)或对,对'-滴滴伊(p'p-DDE)(0-150微克/毫升)存在的情况下进行孵育。然后通过流式细胞术(DNA细胞含量分析)和荧光显微镜(Hoechst染色)测定凋亡情况。与对照组相比,80微克/毫升的滴滴涕、滴滴滴和滴滴伊可诱导显著水平的凋亡,在100微克/毫升时达到最大效应。我们在孵育12小时时开始检测到凋亡,在24小时孵育时达到最大效应。在用三种测试化合物以及100微克/毫升的邻,对'-滴滴涕(o'p-DDT)处理并孵育24小时的细胞中,使用末端脱氧核苷酸转移酶介导的缺口末端标记法(TUNEL法)证实了这些结果。我们的数据表明,滴滴涕及其代谢产物能够在体外诱导人PBMC凋亡。因此,我们对接触这种杀虫剂的儿童进行了一项初步研究。与对照人群相比,接触滴滴涕的儿童血液中滴滴涕、滴滴滴和滴滴伊的水平更高,凋亡频率也更高。在接触滴滴涕的儿童中,发现凋亡频率与接触滴滴涕和滴滴伊之间存在弱正相关。我们的结果表明,对于接触滴滴涕的人群需要开展更多研究,因为凋亡可能会导致诸如免疫抑制等严重的公共卫生影响。