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Metabolism of Retinol and Retinoic Acid in N-Methyl-N-nitrosourea-induced Mammary Carcinomas in Rats¹

Clinical Research Institute of Montreal, Department of Medicine, University of Montreal, Montréal, Québec H2W 1R7, Canada

This study was conducted to examine the in vivo uptake and metabolism of natural retinoids by N-methyl-N-nitrosourea-induced mammary carcinomas. In this study, endogenous retinol and retinyl esters were present in normal mammary epithelial cells, but were undetectable in N-methyl-N-nitrosourea-induced mammary carcinomas in rats as determined by high-pressure liquid chromatography. No differences were found in plasma levels of retinol, in liver retinyl esters, or total content of vitamin A between tumor-bearing and control animals. Administered labeled retinol was taken up and esterified by normal mammary epithelial cells. Tumor-bearing rates were given injections i.p. of either [³H]retinol or [³H]retinoic acid. Radioactivity increased progressively with time in liver and other tissues except in breast tumor, where the uptake fluctuated over the 8 days after the injection of [³H]retinol; in mammary tumors practically no metabolism of [³H]retinol occurred, while in other tissues extensive esterification was detectable. In contrast, in animals given injections of [³H]retinoic acid, the uptake and metabolism of the label in the breast tumors paralleled with those found in other tissues. Neither the activity of acyl coenzyme A:retinol acyl transferase nor the activity of retinyl ester hydrolase was altered in the mammary tumor compared to the normal mammary gland. On the other hand, a significant decrease in the retinal oxidase activity was found in tumor tissue compared to normal mammary tissue. Since no esterification of [³H]retinol occurred in vivo despite the presence of acyl coenzyme A:retinol acyl transferase activity, it is possible that a specific defect in the cellular uptake of retinol may exist in N-methyl-N-nitrosourea-induced mammary carcinomas.

¹ This work was supported by the Medical Research Council of Canada (Grant MA 7328) and by the National Cancer Institute of Canada.

² To whom requests for reprints should be addressed, at Clinical Research Institute of Montreal, 110 Pine Avenue West, Montréal, Québec H2W 1R7, Canada.

Received 4/29/88. Revised 9/ 2/88. Accepted 10/ 3/88.

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