Citation:

Wood, C., M. George, S. Kilburn, T. Moore, AND A. Deangelo. Carryover effects of dichloroacetic acid on hepatic tumorigenesis in mice. Presented at Society of Toxicologic Pathology.

Impact/Purpose:

Present at the Society of Toxicologic Pathology, Boston, MA June 24-28, 2012

Description:

Introduction: Dichloroacetic acid (DCA) is a major by-product of drinking water chlorination. Chronic DCA exposure has been shown to increase liver tumors in mice, although carryover effects and interactions with other promotional agents are not known. Here we evaluated effects of DCA on hepatic tumorigenesis in mice when given alone or prior to phenobarbital (PB), a rodent liver tumor promoter. Methods: The study followed a stop-promotion design in which male and female B6C3F1 mice were divided into the following six treatment groups: deionized water alone (dH2O, control) or with 0.06% phenobarbital (PB); DCA (1.0g/L) for 10 weeks followed by dH2O or PB; and DCA (2.0g/L) for 10 weeks followed by dH2O or PB (n=19-28/group/sex). Male treatments also included DCA (3.5g/L) for 10 weeks followed by water (n=26). Phenobarbital was given for 90 weeks starting at week 10. Pathology assessments were performed at 100 weeks. Results: Liver tumor incidence was significantly increased in all PB-treated groups for male and female mice (p<0.05 vs. respective control groups). In males, DCA stop-treatment alone significantly increased liver tumor incidence only at the 3.5g/L dose (p<0.05 vs. control). In female mice, DCA stop-treatment alone increased liver tumor incidence at 1.0g/L and 2.0g/L doses (p<0.05 for both vs. control). Treatment with DCA prior to PB did not increase tumor incidence beyond PB alone. Discussion: Subchronic exposure to DCA in drinking water resulted in long-term carryover effects on hepatic tumorigenesis in male and female mice. Prior treatment with DCA did not enhance tumor-promoting effects of PB.

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