In vivo use of N-(4-hydroxyphenyl retinamide)-0-glucuronide as a breast cancer chemopreventive agent.
The inhibitory effects of N-(4-hydroxyphenyl) retinamide and its glucuronide derivative on the development and growth of 7,12-dimethylbenz (a) anthracene - induced rat mammary tumors in vivo were compared. The results indicate that the glucuronide had a greater chemopreventive potency than equimolar concentration of the free retinoid by all the criteria measured, mainly the inhibition of tumor incidence, multiplicity and tumor growth. HPLC analysis of the blood of the rats showed no hydrolysis of the glucuronide during its chronic consumption, indicating that the retinoid glucuronide is probably acting in vivo per se rather than through hydrolysis to the free retinoid. The higher potency and lower toxicity of the glucuronide suggests, for the first time, that the conjugate may have an in vivo chemopreventive advantage over the parent retinamide.
Abou-Issa
H
H
Department of Surgery, College of Medicine, Ohio State University, Columbus 43210.
Curley
R W
RW
Panigot
M J
MJ
Wilcox
K A
KA
Webb
T E
TE
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D004354:Drug Screening Assays, Antitumor; D005260:Female; D017313:Fenretinide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005965:Glucuronates / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005965:Glucuronates; C084238:N-((4-hydroxyphenyl)retinamide)-O-glucuronide; D017313:Fenretinide; D015127:9,10-Dimethyl-1,2-benzanthracene