Effect of retinyl acetate and 4-hydroxyphenylretinamide on initiation of chemically-induced mammary tumors.
The anti-promotional effect of retinoids on chemically-induced mammary carcinogenesis in the rat is well established. The present studies were performed to determine the effect of long-term feeding of retinyl acetate and 4-hydroxyphenylretinamide (4-HPR) on initiation of mammary tumors induced by MNU or DMBA. Retinyl acetate (328 mg/kg of diet) or 4-HPR (782 mg/kg of diet) was added to the diet of female Sprague-Dawley rats for two months prior to the administration of the carcinogens. In the MNU model, a 50% increase in the number of mammary adenocarcinomas was observed in rats pretreated with retinyl acetate, while pretreatment with 4-HPR resulted in a 93% increase in the number of cancers. Continued treatment with 4-HPR throughout the study, however, caused a reduction in cancer number. In the DMBA mode, pretreatment with these retinoids significantly increased the number of benign mammary tumors, but not mammary cancers. These data suggest that newly synthesized retinoids should be evaluated for chemopreventive activity against mammary cancer initiation as well as for their anti promotional activity.
Grubbs
C J
CJ
Department of Nutrition Sciences, University of Alabama, Birmingham 35294.
Eto
I
I
Juliana
M M
MM
Hardin
J M
JM
Whitaker
L M
LM
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D004224:Diterpenes; D005260:Female; D017313:Fenretinide; D008099:Liver / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D008770:Methylnitrosourea / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D000084562:Retinyl Esters; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; D017313:Fenretinide; C009166:retinol acetate; D014212:Tretinoin; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea