Promotion by 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 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 (MNU). The mice were administered the chloroacetic acids in drinking water starting at 7 weeks of age and continuing until sacrificed 31 or 52 weeks later. Both chloroacetic acids promoted MNU-initiated foci and tumors, however their concentration-response relationships differed being exponential and linear for DCA or TCA, respectively. Lesions promoted by DCA but not TCA, regressed upon termination of exposure at 31 weeks. Foci and tumors promoted by DCA were eosinophilic and contained glutathione S-transferase-π (GST-π), while TCA promoted basophilic tumors lacking GST-π. Hence, tumor promotion by DCA and TCA appeared to differ both with respect to their concentration-response relationships and to the characteristics of precancerous lesions and tumors.