TY - JOUR
T1 - Evaluation of the antitumour activity of the non-steroidal antioestrogen monohydroxytamoxifen in the DMBA* * DMBA; 7,12-dimethylbenz(a)anthracene.-induced rat mammary carcinoma model
AU - Jordan, V. C.
AU - Allen (née Naylor), Karen E.
N1 - Funding Information:
*DMBA; 7, l 2-dimethylbenz(a)anthracene. ~Supported by grants from ICI Ltd (Pharmaceuticals Division ) and the Yorkshire Cancer Research Campaign. ++Present address and reprint requests: Ludwig Institute for Cancer Research, Inselspital, Bern, Switzerland.
PY - 1980/2
Y1 - 1980/2
N2 - The antitumour activity of monohydroxytamoxifen has been compared with tamoxifen in the DMBA-induced rat mammary carcinoma model. In general antioestrogen therapy between 30 and 60 days after DMBA administration was more successful than therapy between 60 and 90 days after DMBA. Although monohydroxy-tamoxifen was a more potent antioestrogen than tamoxifen and equivalent dosage regimens were more effective at reducing cytoplasmic oestrogen receptor concentrations in the ovariectomized rat uterus, tamoxifen appeared to be a more potent antitumour agent. The administration of 4 weekly courses of tamoxifen (0.2, 3, 50 or 800 μg daily, 5 times a week) starting 30 days after DMBA produced a dose-related delay in tumour appearance and a decrease in tumour numbers. By contrast, monohydroxytamoxifen (0.012, 0.2, 3 or 50 μg daily, 5 times a week) was only weakly active at delaying tumour appearance although tumour numbers were reduced. Most of the tumours that developed in groups previously treated with antioestrogens regressed upon ovariectomy of the host. From studies in ovariectomized rats, tamoxifen was found to have long term effects upon the uterus whereas equivalent doses of monohydroxytamoxifen were only effective for a short period after the cessation of therapy. These data suggest that mammary tumour development is best inhibited in the constant presence of an antioestrogen i.e., biological half-life, as well as potency, is important for antitumour activity. The principle was exemplified by a reduction in the number and sizes of mammary tumours developing during continuous therapy with monohydroxytamoxifen (3 or 50 μg daily, 5 times a week) starting 30 days after DMBA. Overall it was clear that antioestrogens do not destroy all the foci of hormone dependent tumour cells and long courses of therapy or the use of other antihormonal methods e.g., ovariectomy, are essential to control tumour growth.
AB - The antitumour activity of monohydroxytamoxifen has been compared with tamoxifen in the DMBA-induced rat mammary carcinoma model. In general antioestrogen therapy between 30 and 60 days after DMBA administration was more successful than therapy between 60 and 90 days after DMBA. Although monohydroxy-tamoxifen was a more potent antioestrogen than tamoxifen and equivalent dosage regimens were more effective at reducing cytoplasmic oestrogen receptor concentrations in the ovariectomized rat uterus, tamoxifen appeared to be a more potent antitumour agent. The administration of 4 weekly courses of tamoxifen (0.2, 3, 50 or 800 μg daily, 5 times a week) starting 30 days after DMBA produced a dose-related delay in tumour appearance and a decrease in tumour numbers. By contrast, monohydroxytamoxifen (0.012, 0.2, 3 or 50 μg daily, 5 times a week) was only weakly active at delaying tumour appearance although tumour numbers were reduced. Most of the tumours that developed in groups previously treated with antioestrogens regressed upon ovariectomy of the host. From studies in ovariectomized rats, tamoxifen was found to have long term effects upon the uterus whereas equivalent doses of monohydroxytamoxifen were only effective for a short period after the cessation of therapy. These data suggest that mammary tumour development is best inhibited in the constant presence of an antioestrogen i.e., biological half-life, as well as potency, is important for antitumour activity. The principle was exemplified by a reduction in the number and sizes of mammary tumours developing during continuous therapy with monohydroxytamoxifen (3 or 50 μg daily, 5 times a week) starting 30 days after DMBA. Overall it was clear that antioestrogens do not destroy all the foci of hormone dependent tumour cells and long courses of therapy or the use of other antihormonal methods e.g., ovariectomy, are essential to control tumour growth.
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U2 - 10.1016/0014-2964(80)90156-5
DO - 10.1016/0014-2964(80)90156-5
M3 - Article
C2 - 6768559
AN - SCOPUS:0018906517
SN - 0014-2964
VL - 16
SP - 239
EP - 251
JO - European Journal of Cancer (1965)
JF - European Journal of Cancer (1965)
IS - 2
ER -