DNA damage and G2/M arrest in Syrian hamster embryo cells during Malachite green exposure are associated with elevated phosphorylation of ERK1 and JNK1.
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.
Bose
Bipasha
B
Chemical Carcinogenesis Group, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410 208, India.
Motiwale
Leena
L
Rao
K V K
KV
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents / Q000633:toxicity*; D020552:Comet Assay; D006224:Cricetinae; D004249:DNA Damage; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D016195:G2 Phase / Q000187:drug effects; D008647:Mesocricetus / Q000196:embryology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D012394:Rosaniline Dyes / Q000633:toxicity*
D000891:Anti-Infective Agents, Local; D004396:Coloring Agents; D012394:Rosaniline Dyes; C005095:malachite green; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8