Abstract |
TAT-59 suppressed the growth of DMBA-induced mammary tumors in rats earlier and more strongly than tamoxifen (TAM). After oral administration of the drugs, DP-TAT-59, one of the main metabolites of TAT-59, was found in 10- to 15-fold higher concentrations in both the tumor and blood compared to 4-OH-TAM, an active metabolite of TAM. In a 3-day antiuterotrophic test, every detected metabolite of TAT-59 showed stronger antiestrogenic activity than did TAM. In a competition assay, the affinity of the metabolites for estrogen receptors ranged from that of estradiol to that of TAM. These results suggest that the superior antiestrogenic activity of TAT-59 compared to TAM was either due to its higher penetration into tumor tissue or to the stronger antiestrogenic activity of its metabolites.
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Authors | T Toko, J Shibata, Y Sugimoto, H Yamaya, M Yoshida, K Ogawa, E Matsushima |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 37
Issue 1-2
Pg. 7-13
( 1995)
ISSN: 0344-5704 [Print] Germany |
PMID | 7497599
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Antineoplastic Agents, Hormonal
- Estrogen Antagonists
- Receptors, Estrogen
- Tamoxifen
- TAT 59
- Estradiol
- 9,10-Dimethyl-1,2-benzanthracene
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Topics |
- 9,10-Dimethyl-1,2-benzanthracene
- Animals
- Antineoplastic Agents, Hormonal
(pharmacokinetics)
- Binding, Competitive
- Estradiol
(metabolism)
- Estrogen Antagonists
(pharmacokinetics)
- Female
- Mammary Neoplasms, Experimental
(chemistry, drug therapy)
- Rats
- Rats, Sprague-Dawley
- Receptors, Estrogen
(analysis)
- Tamoxifen
(analogs & derivatives, pharmacokinetics, therapeutic use)
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