Metabolism of retinol and retinoic acid in N-methyl-N-nitrosourea-induced mammary carcinomas in rats.
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 rats 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.
Bhat
P V
PV
Department of Medicine, University of Montreal, Québec, Canada.
Lacroix
A
A
D000217:Acyltransferases / Q000032:analysis; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000032:analysis; D005260:Female; D008099:Liver / Q000032:analysis; D008321:Mammary Glands, Animal / Q000032:analysis / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008770:Methylnitrosourea; D051381:Rats; D011919:Rats, Inbred Strains; D051142:Retinol O-Fatty-Acyltransferase; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000032:analysis / Q000378:metabolism*
D014801:Vitamin A; D014212:Tretinoin; D008770:Methylnitrosourea; D000217:Acyltransferases; D051142:Retinol O-Fatty-Acyltransferase; D002265:Carboxylic Ester Hydrolases; C022523:retinyl esterase