Metabolism of retinol and retinoic acid in N-methyl-N-nitrosourea-induced mammary carcinomas in rats.

Abstract

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.

• Authors: P V Bhat, A Lacroix
• Journal: Cancer research (Cancer Res) Vol. 49 Issue 1 Pg. 139-44 (Jan 01 1989) ISSN: 0008-5472 [Print] United States
• PMID: 2908841 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Vitamin A
• Tretinoin
• Methylnitrosourea
• Acyltransferases
• Retinol O-Fatty-Acyltransferase
• Carboxylic Ester Hydrolases
• retinyl esterase

Topics

• Acyltransferases (analysis)
• Animals
• Carboxylic Ester Hydrolases (analysis)
• Female
• Liver (analysis)
• Mammary Glands, Animal (analysis, metabolism)
• Mammary Neoplasms, Experimental (chemically induced, metabolism)
• Methylnitrosourea
• Rats
• Rats, Inbred Strains
• Retinol O-Fatty-Acyltransferase
• Tretinoin (metabolism)
• Vitamin A (analysis, metabolism)