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In Vivo Stimulation of DNA Synthesis and Induction of Ornithine Decarboxylase in Rat Colon by Fatty Acid Hydroperoxides, Autoxidation Products of Unsaturated Fatty Acids¹

Departments of Chemistry [A. W. B., L. J. M.], Surgery [N. D. N., W. A. G.], and Pathology [J. D. C.], Wayne State University, School of Medicine, Detroit, Michigan 48201

The effect of intrarectal instillation of hydroperoxy and hydroxy fatty acids on colonic DNA synthesis and ornithine decarboxylase activity in male Sprague-Dawley rats was examined. A mixture of hydroperoxy-arachidonic acid isomers was prepared by methylene blue-sensitized photooxygenation. Pure 13-hydroperoxy-9,11-octadecadienoic acid was prepared by the action of soybean lipoxygenase on linoleic acid. Sodium borohydride reduction yielded the respective hydroxy fatty acids. Twelve hr after instillation of solutions of either hydroperoxy or hydroxy fatty acids, at concentrations up to 10 mM, DNA synthesis was increased in a dose-dependent fashion up to 240% above control values. The induction of omithine decarboxylase occurred over a similar concentration range 3 hr after instillation of oxidized linoleic acid. In this case, the hydroxy acids (49-fold increase at 10 mM), were more stimulatory than the hydroperoxy derivatives (23-fold at 10 mM). Highly purified linoleic and arachidonic acids did not stimulate either activity at concentrations up to 50 mM. These data indicate that autoxidation products of unsaturated fatty acids, likely components of high-fat diets, can evoke proliferative responses in colonic mucosa. These responses may be relevant to the promotional effect of high dietary fat on colon carcinogenesis.

¹ This work was supported by the James and Lynelle Holden Fund.

² Recipient of a Faculty Research Award from the American Cancer Society (FRA 243). To whom requests for reprints should be addressed.

Received 3/15/84. Accepted 8/10/84.

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