Stimulation of DNA synthesis in primary rat hepatocyte cultures by metanil yellow: a new liver tumour promoter.

In order to understand the possible mechanism(s) by which metanil yellow (MY) promotes liver tumour development, we have studied the effect of MY on DNA synthesis in primary cultures of normal rat hepatocytes, maintained under fully-defined conditions. MY alone was moderate, however, in combination with epidermal growth factor (EGF) showed synergism in markedly stimulating DNA synthesis which was dose-dependent. MY also showed stimulation of DNA synthesis either when added 16 h after the hepatocytes were primed with EGF or when first primed with MY for 16 h and then EGF was added. These observations suggest that the target site for MY action may be at the level of EGF-receptor of EGF-mediated early events. Further, MY induced DNA stimulation was found to be independent of insulin and dexamethasone. These results indicate that an important component of the tumour enhancement by MY may be its ability to cause an exaggerated version of the stimulation of DNA synthesis.