Effect of tamoxifen and D,L-2-difluoromethylornithine on the growth, ornithine decarboxylase activity and polyamine content of mammary carcinomas induced by 1-methyl-1-nitrosourea.
The effect of combined treatment with D,L-2-difluoromethylornithine (DFMO) and tamoxifen on the growth status, ornithine decarboxylase (ODC) activity and polyamine content of established 1-methyl-1-nitrosourea (MNU)-induced mammary tumors was investigated. DFMO treatment, a 0.125% solution provided as drinking water, inhibited the rate of tumor occurrence and reduced the number of mammary tumors induced by a high dose of MNU (50 mg/kg body weight) during the first 120 days post-carcinogen treatment. Tamoxifen was administered daily via s.c. injection (25 micrograms/100 g body weight) to tumor-bearing rats in both treatment groups, i.e. control and DFMO-treated, for a 30-day period beginning 120 days after carcinogen. Tamoxifen treatment induced tumor regression but the percentage of regressing, static or growing tumors was no different in the presence or absence of DFMO. Whereas the mammary tumors of DFMO-treated rats had reduced ODC activity and lower polyamine concentrations in comparison to the tumors of untreated animals, tamoxifen had no effect on these parameters independent of its effect on tumor growth status. DFMO did not increase the efficacy of tamoxifen in inducing tumor regression.
Thompson
H J
HJ
Ronan
A M
AM
Ritacco
K A
KA
Meeker
L D
LD
D000818:Animals; D000518:Eflornithine; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000032:analysis / Q000139:chemically induced / Q000188:drug therapy*; D008770:Methylnitrosourea; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009955:Ornithine Decarboxylase / Q000032:analysis*; D011073:Polyamines / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*
D011073:Polyamines; D013629:Tamoxifen; D008770:Methylnitrosourea; D009952:Ornithine; D009955:Ornithine Decarboxylase; D000518:Eflornithine