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The effect of tamoxifen on reverse transcriptase production from monocytes of patients with breast cancer.


Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;:132.

It has been previously shown that monocytes from patients with breast cancer contain a retrovirus. Tamoxifen is a well known drug used for the treatment of breast cancer. The mode of action of this agent is unclear. This study was designed to investigate the effect of tamoxifen on the viral release from monocytes obtained from patients with primary breast cancer. Peripheral blood monocytes from 24 patients with stage I or stage II malignancies were incubated in Eagle's medium supplemented with 10 per cent foetal calf serum, and 330 ng/ml phorbole myristate acetate, paralleled cultures were set up with 300 ng/ml tamoxifen. After 6 days incubation, the supernatant was centrifuged at 600 g for 30 minutes, filtered through 220 nm micropore filter. The filtrate was centrifuged at 100,000 g for 1 h. The pellet was suspended in TNE buffer. Reverse transcriptase (RT) activity was assayed using a standard method. Tamoxifen significantly (p less than 0.0001 Student's t test) inhibited RT activity. With no tamoxifen RT activity was 378+/-8 (mean, SEM) pmol dCTP incorporated and with tamoxifen the activity was 147+/-12 (mean, SEM). Taking a cut-off for positivity of 25 pmol of dCTP incorporated/million monocytes, the activity was completely inhibited in 15 out of 24 patients. This study strongly supports our previous observations which suggest the presence of a retrovirus in monocytes from patients with breast cancer, and that tamoxifen has the capability of inhibiting RT activity. Furthermore, this technique can be used as a simple test for the responsiveness of patients with breast cancer to the drug.

Codon Human HIV-1/*DRUG EFFECTS/ENZYMOLOGY Microbial Sensitivity Tests Mutation Pyrimidines/*PHARMACOLOGY RNA-Directed DNA Polymerase/GENETICS Serial Passage ABSTRACT


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