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Assessment of hepatic initiation-promotion properties of trichloroacetic acid

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Abstract

The ability of trichloroacetic acid (TCA) to act as an initiator or promoter of carcinogenesis was studied in the γ-glutamyl transpeptidase (GGT) enzyme altered foci (EAF) assay, using the rat partial hepatectomy model and diethylnitrosamine (DEN) phenobarbital (PB) positive controls. The capacity of TCA to induce peroxisomal proliferation was examined by measuring the induction of hepatic peroxisomal-dependent14C-palmitoyl-CoA. Induction of hepatic ornithine decarboxylase (ODC) was also measured.

No evidence of initiating activity by TCA was evident in male Sprague-Dawley rats by the EAF assay. However, a significant increase in numbers and size of GGT-positive foci compared to controls were observed in rats exposed to 50, 500 or 5,000 mg/L TCA as a promoter for 3–12 months in the drinking water following initiation with DEN. A significant, though weak (10–20% over controls), stimulation of hepatic peroxisomal-dependent14C-palmitoyl-CoA was seen only in groups of rats promoted with TCA at 5,000 mg/L. A single large dose (1,500 mg/kg) of TCA produced a significant (26–70 fold) increase in hepatic ornithine decarboxylase activity 5 and 18 hr after administration. No changes in organ/body weights or significant histopathological lesions could be attributed to TCA exposure. These data suggest TCA possesses promoting activity in the rat hepatic model system. However, there was no dose-related correlation between the very weak peroxisomal proliferating effect and promoting activity.

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Authors and Affiliations

  1. National Center for Toxicological Research, 72079, Jefferson, Arkansas

    Michael J. Parnell

  2. Department of Veterinary Medicine, University of Idaho, 83843, Moscow, Idaho

    Jerry H. Exon

  3. Office of the Dean, College of Veterinary Medicine, Oregon State University, 97331, Corvallis, Oregon

    Loren D. Koller

Authors
  1. Michael J. Parnell
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  2. Jerry H. Exon
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  3. Loren D. Koller
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Supported by US EPA Cooperative Agreement No. CR811905.

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Parnell, M.J., Exon, J.H. & Koller, L.D. Assessment of hepatic initiation-promotion properties of trichloroacetic acid. Arch. Environ. Contam. Toxicol. 17, 429–436 (1988). https://doi.org/10.1007/BF01055507

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  • DOI: https://doi.org/10.1007/BF01055507

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