Chemopreventive effects of the aromatase inhibitors vorozole (R-83842) and 4-hydroxyandrostenedione in the methylnitrosourea (MNU)-induced mammary tumor model in Sprague-Dawley rats.
The chemopreventive activity of the aromatase inhibitors vorozole and 4-hydroxyandrostenedione were determined in the methylnitrosourea (MNU)-induced model of rat mammary tumorigenesis. Vorozole (5 and 2.5 mg/kg body wt) and 4-hydroxyandrostenedione (15 and 6 mg/rat) were administered daily (by gavage) to virgin female Sprague-Dawley rats starting at an age of 43 days. Seven days later animals were given a single dose of MNU. Following treatment with MNU, animals continued to be treated with vorozole and 4-hydroxyandrostenedione daily until the end of the experiment (100 days post MNU treatment). Vorozole at either dose proved to be a profound inhibitor of MNU-induced mammary tumors. Vorozole decreased tumor incidence from 100% to 10%, while simultaneously decreasing tumor multiplicity from 5 tumors per animal to 0.1 tumors per animal. This chemopreventive effect was accompanied by significant increases in body weight gain in the animals treated with vorozole when compared with control rats. In contrast, neither dose of 4-hydroxyandrostenedione had any effect on tumor incidence and only the higher dose slightly decreased tumor multiplicity.
Lubet
R A
RA
NCI-DCPC, Bethesda, MD 20892.
Steele
V E
VE
Casebolt
T L
TL
Eto
I
I
Kelloff
G J
GJ
Grubbs
C J
CJ
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control*; D000616:Aminoglutethimide / Q000494:pharmacology; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D047072:Aromatase Inhibitors; D004354:Drug Screening Assays, Antitumor; D004971:Estrus / Q000187:drug effects; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008770:Methylnitrosourea; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D047072:Aromatase Inhibitors; D014230:Triazoles; D000616:Aminoglutethimide; C060523:vorozole; D000735:Androstenedione; D008770:Methylnitrosourea; C014594:formestane