Tamoxifen-Induced Chromosomal Aberrations in Pregnant Female Rats

Abstract

Tamoxifen is a non-steroidal, selective estrogen receptor modulator (SERM) used in the treatment of all the stages of breast cancer patients at all ages. Recent evidences showed that tamoxifen could induce cancers which might be a consequent result for chromosomal aberrations in rats. For investigating the chromosomal aberrations induced by tamoxifen treatment, pregnant female rats (four rats per treatment) received tamoxifen orally at dose 0 and 20 mg/ kg b. wt. at different periods. Animals were injected (ip.) with colchicine at 1.5 hr prior sacrifice. Rats were sacrificed 24hr after last treatment. bone marrow cells where collected, then the cells were prepared for karyotype evaluation. 50 well spread metaphase plates were examined per animal. Tamoxifen induced significant increases in the frequencies of structural chromosomal aberrations, like gaps, Centric fragments, dicentirc chromosomes, centric separation and centric fusions in the bone marrow metaphases. However, tamoxifen did not elevate the averages of numerical chromosomal aberrations than the averages of control level. Moreover, a significant increase in the mitotic activity of the bone marrow cells was observed after tamoxifen treatment. The present study proved the clastogenic and the spindle poisoning action of tamoxifen. Consequently, risks against benefits should be carefully evaluated when tamoxifen is used as a therapy of choice on humans.