Ren X H, Lu W X, Chen Z H, Liu W, Wang S Q, Luo N Y, Liu J J
Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2018 Jul 20;36(7):481-484. doi: 10.3760/cma.j.issn.1001-9391.2018.07.001.
To investigate DNA damage in the transformed human bronchial epithelial cells (16HBE) induced by hexavalent chromium (Cr(6+)) and further elucidate the potential carcinogenesis mechanism of Cr(6+). 16HBE were treated with different concentration of Cr(6+ ()0, 0.625, 1.25, 2.5 μmol/L) for 15 weeks. The malignant degrees of transformed cells were identified by the assays for anchorage-independent growth and tumorigenicity. According to the single cell gel electrophoresis (SCGE) assay, the DNA damage rate was calculated. The expression level of 53BP1 was determined by Western blot. Chromium-treated cells could form colonies in soft agar and tumors in nude mice. Compared with the control group, colony formation efficiency of 1.25μmol/L and 2.5 μmol/L Cr(6+)-treated cells in soft agar showed significant increases (p<0.05) . The 2.5 μmol/L Cr(6+)-treated cells also formed tumors subcutaneously in nude mice. Cr(6+) could cause different degree of DNA damage to 16HBE cells in a dose-dependent manner. In addition, Western blot analyses showed that 53BP1 was aberrantly down-regulated at 2.5 μmol/L dose and has no significant changes at 0.625 μmol/L and 1.25 μmol/L dose under the treatment of Cr(6+). The declined expression of 53BP1 may mediate Cr(6+)-induced DNA damage and further involved in the cell malignant transformation.
为研究六价铬（Cr(6+)）诱导的人支气管上皮转化细胞（16HBE）中的DNA损伤，并进一步阐明Cr(6+)潜在的致癌机制。将16HBE细胞用不同浓度的Cr(6+)（0、0.625、1.25、2.5 μmol/L）处理15周。通过非锚定依赖性生长和致瘤性检测鉴定转化细胞的恶性程度。根据单细胞凝胶电泳（SCGE）检测计算DNA损伤率。通过蛋白质免疫印迹法测定53BP1的表达水平。经铬处理的细胞可在软琼脂中形成集落，并在裸鼠体内形成肿瘤。与对照组相比，1.25 μmol/L和2.5 μmol/L Cr(6+)处理的细胞在软琼脂中的集落形成效率显著增加（p<0.05）。2.5 μmol/L Cr(6+)处理的细胞也可在裸鼠皮下形成肿瘤。Cr(6+)可对16HBE细胞造成不同程度的DNA损伤，且呈剂量依赖性。此外，蛋白质免疫印迹分析显示，在Cr(6+)处理下，53BP1在2.5 μmol/L剂量时异常下调，在0.625 μmol/L和1.25 μmol/L剂量时无显著变化。53BP1表达的下降可能介导Cr(6+)诱导的DNA损伤，并进一步参与细胞恶性转化。
