Bose Bipasha, Motiwale Leena, Rao K V K
Chemical Carcinogenesis Group, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410 208, India.
Cancer Lett. 2005 Dec 18;230(2):260-70. doi: 10.1016/j.canlet.2005.01.001.
Malachite Green (MG), consisting of green crystals with a metallic luster, is highly soluble in water, cytotoxic to various mammalian cells and also acts as a liver tumor promoter. In view of its industrial importance and possible exposure to human beings, MG poses a potential environmental health hazard. We have earlier reported the malignant transformation of Syrian hamster embryo (SHE) cells in primary culture by MG. In this study, we have studied the ability of MG to cause DNA damage, cell cycle arrest, apoptosis and possible roles of ERK, JNK and p38 MAP kinases. Exposure of SHE cells to MG causes DNA damage. Flow cytometric analysis showed an increase of G2/M phase and apoptotic cells in MG treated cells compared to control SHE cells. Western blots of MG treated cells with phosphoactive antibodies showed elevated phosphorylation of ERK1 and JNK1 and no change in p38 kinase. However, total forms of ERKs, JNKs and p38 kinases showed similar levels of expression in control and MG treated SHE cells. The present study indicates that elevated phosphorylation of ERK1 and JNK1 and an increase in G2/M phase and apoptotic cells seems to be the changes associated with MG exposure to SHE cells in primary culture.
孔雀石绿(MG)由具有金属光泽的绿色晶体组成,极易溶于水,对各种哺乳动物细胞具有细胞毒性,并且还可作为肝肿瘤促进剂。鉴于其工业重要性以及可能对人类造成的接触,MG构成了潜在的环境健康危害。我们之前曾报道过原代培养的叙利亚仓鼠胚胎(SHE)细胞被MG恶性转化的情况。在本研究中,我们研究了MG导致DNA损伤、细胞周期停滞、凋亡的能力以及细胞外信号调节激酶(ERK)、应激活化蛋白激酶(JNK)和p38丝裂原活化蛋白激酶(MAP激酶)的可能作用。将SHE细胞暴露于MG会导致DNA损伤。流式细胞术分析显示,与对照SHE细胞相比,经MG处理的细胞中G2/M期细胞和凋亡细胞增加。用磷酸化活性抗体对经MG处理的细胞进行蛋白质免疫印迹分析显示,ERK1和JNK1的磷酸化水平升高,而p38激酶无变化。然而,ERK、JNK和p38激酶的总形式在对照和经MG处理的SHE细胞中表达水平相似。本研究表明,ERK1和JNK1磷酸化水平升高以及G2/M期细胞和凋亡细胞增加似乎是原代培养的SHE细胞暴露于MG所伴随的变化。