Promotion by mixtures of dichloroacetic acid and trichloroacetic acid of N-methyl-N-nitrosourea-initiated cancer in the liver of female B6C3F1 mice

Hepatic tumor promoting activity was determined for mixtures of dichloroacetic acid (DCA) and trichloroacetic acid (TCA) in female B6C3F1 mice initiated on day 15 of age with 25 mg/kg N-methyl-N-nitrosourea. The mice received in their drinking water from 6 to 50 weeks of age either DCA (7.8, 15.6, or 25 mmol/l) with/without 6.0 mmol/l TCA or TCA (6.0 or 25 mmol/l) with/without 15.6 mmol/l DCA. Proliferative lesions (foci of altered hepatocytes and hepatocellular adenomas) promoted by TCA increased linearly with its concentration and were predominantly basophilic and negative for glutathione S-transferase-pi (GST-pi), while those promoted by DCA increased exponentially with its concentration and were eosinophilic and positive for GST-pi. The promoting activity of DCA and TCA in mixtures was at least additive. The proliferative lesions resulting from exposure to the mixtures were predominately similar to those promoted by DCA, i.e. contained eosinophilic and GST-pi-positive hepatocytes. (C) 1997 Elsevier Science Ireland Ltd.