Rao K V
Cellular Carcinogenesis Laboratory, Tata Memorial Centre, Parel, Bombay, India.
Toxicol Lett. 1995 Nov 15;81(2-3):107-13. doi: 10.1016/0378-4274(95)03413-7.
Malachite green (MG), a triarylmethane dye is highly cytotoxic to mammalian cells and also acts as a liver tumour-enhancing agent. In view of its industrial importance and possible exposure to individuals, MG may pose a potential environmental health hazard. The mechanism(s) by which MG enhances DEN-induced liver carcinogenesis is still unknown even though growth modulatory effects appear to be important in its action. Therefore, we have studied the effect of MG on DNA synthesis in primary cultures of normal adult rat hepatocytes maintained under fully defined conditions. The rate of DNA synthesis in both untreated and hepatocytes treated with epidermal growth factor (10 ng/ml) were inhibited by MG at concentrations of 0.025-0.4 micrograms/ml. These inhibitory effects were concomitant with an extensive release of lactate dehydrogenase which began after 24 h. MG inhibited DNA synthesis when added after only 16 h in hepatocytes either primed or not primed with EGF, suggesting that the target site may be other than the EGF-receptor or EGF-mediated early events involving signal transduction. The present study indicates that cytotoxic and mitoinhibitory properties of MG possibly play an important role during tumour promotion.
孔雀石绿（MG）是一种三芳基甲烷染料，对哺乳动物细胞具有高度细胞毒性，还可作为肝肿瘤促进剂。鉴于其工业重要性以及可能对个体造成的接触，MG可能构成潜在的环境健康危害。尽管生长调节作用在其作用中似乎很重要，但MG增强二乙基亚硝胺（DEN）诱导的肝癌发生的机制仍不清楚。因此，我们研究了MG对在完全确定的条件下培养的正常成年大鼠原代肝细胞中DNA合成的影响。在浓度为0.025 - 0.4微克/毫升时，MG抑制了未处理的肝细胞以及用表皮生长因子（10纳克/毫升）处理的肝细胞中的DNA合成速率。这些抑制作用伴随着24小时后乳酸脱氢酶的大量释放。在肝细胞中，无论是否用表皮生长因子预处理，MG仅在加入16小时后就抑制了DNA合成，这表明靶位点可能不是表皮生长因子受体或涉及信号转导的表皮生长因子介导的早期事件。本研究表明，MG的细胞毒性和有丝分裂抑制特性可能在肿瘤促进过程中起重要作用。
