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The Effects of Hepatotoxic Agents and of Liver Growth on the Urinary Excretion of the N-Hydroxy Metabolite of 2-Acetylaminofluorene by Rats^*

Alfredo Margreth, Prabhakar D. Lotlikar, Elizabeth C. Miller and James A. Miller

( McArdle Memorial Laboratory for Cancer Research, Medical School, University of Wisconsin, Madison, Wis.)

Adult rats subjected to a number of treatments which cause liver damage and/or growth (administration of hepatotoxic agents, partial hepatectomy, or protein depletion-repletion) and young growing rats excreted in the urine a greater percentage of a test dose of 2-acetylaminofluorene (AAF) as the carcinogenic N-hydroxy metabolite than did normal adult rats. Alterations in the urinary excretion of the noncarcinogenic ring-hydroxy derivatives of AAF under these conditions were much smaller and, in most cases, negligible.

Rats fed certain thermally oxidized derivatives of corn oil excreted 1–2 times as much N-hydroxy-AAF in the urine after a test dose of AAF as rats fed fresh corn oil. These effects are correlated with the increased carcinogenicity of AAF when fed with the thermally oxidized products (Sugai et al.).

^* This investigation was supported by a research training grant, CRTY-5002, and by Grant C355 of the National Cancer Institute, United States Public Health Service; by a grant from the Jane Coffin Childs Memorial Fund for Medical Research; and by the Alexander and Margaret Stewart Trust Fund.

Present address: Institute of General Pathology, University of Padua, Italy. A part of this work was carried out while Dr. Margreth was a Fellow of the Rotary Foundation.

Received 2/ 4/64.