Inhibition of DNA synthesis in primary rat hepatocyte cultures by malachite green: a new liver tumor promoter.

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.