Chemoprevention of MNU-induced mammary tumorigenesis by hormone response modifiers: toremifene, RU 16117, tamoxifen, aminoglutethimide and progesterone.
The effects of structurally different antiestrogens, progesterone and the aromatase inhibitor aminoglutethimide, were evaluated for chemopreventive activity in the N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis model. Treatment with either RU 16117, progesterone or aminoglutethimide resulted in a significant decrease in cancer multiplicity [> or = 50%; P < .05] when administered individually at doses 80% of the maximally tolerated dose [MID]. Toremifene was also remarkably effective in inhibiting MNU-induced mammary tumorigenesis although this inhibition was achieved at a dose which caused a significant decrease in body weight gain. Aminoglutethimide, RU 16117 and toremifene citrate, in addition to their effects on tumor multiplicity, caused significant increases in the latency period for tumor development. Combinations of aminoglutethimide, progesterone and/or a suboptimal dose of tamoxifen citrate also proved to be effective in inhibiting the development of MNU-induced mammary cancers; however, the combination regimen was no more effective than either aminoglutethimide or progesterone administered alone. These results suggested that agents altering the hormonal environment, regardless of their mechanism of action, may provide protection against the development of hormone responsive mammary cancer.
Moon
R C
RC
IIT Research Institute, Chicago, IL 60616.
Steele
V E
VE
Kelloff
G J
GJ
Thomas
C F
CF
Detrisac
C J
CJ
Mehta
R G
RG
Lubet
R A
RA
D000616:Aminoglutethimide / Q000627:therapeutic use*; D000818:Animals; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008770:Methylnitrosourea; D011374:Progesterone / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000627:therapeutic use*; D017312:Toremifene / Q000627:therapeutic use*
D004965:Estrogen Antagonists; D013629:Tamoxifen; D000616:Aminoglutethimide; D004997:Ethinyl Estradiol; D011374:Progesterone; D008770:Methylnitrosourea; C011310:moxestrol; D017312:Toremifene