EMBRYOLOGICAL, CYTOGENETICAL AND MOLECULAR STUDIES ON TAMOXIFEN TREATMENT IN ALBINO RATS

Abstract

The present study had been performed to investigate the adverse effects of tamoxifen treatment on the pregnant rats and their fetuses by investigating the maternal body weights during pregnancy, abortion rates and percentage of resorption. The fetuses were investigated morphologically for any teratological changes in the shape as well as their mortality rates. Rats were also investigated cytogenetically by scoring metaphases spread from the bone marrow of the pregnant mothers for any numerical and/or structural abnormalities. Molecular studies as well were performed by investigating the effect of tamoxifen on the expression of the tumor suppressor p53 gene. Forty virgin fertile female Sprague Dawely rats weighing from 150-180 gm. and ten male rats of the same strain were used. Females were divided into four groups, The first is the control group receiving distilled water throughout the experiment. Group (2) females received a daily oral dose of 20 mg/ kg/ b. wt. tamoxifen for twenty-one days before mating, then mated with untreated males and then dissected at the 20th day of gestation. Group (3) pregnant females received daily oral dose of 20 mg/ kg/ b. wt. tamoxifen from the 7th day of gestation till the 19th day and then dissected at the 20th day. Group (4) females received daily Summary Summary Page 125 oral dose of 20 mg/ kg/ b. wt. tamoxifen from the 7th day till the 20th day of gestation and delivers normally. The tamoxifen doses are related to tamoxifen therapeutic doses. The results reveals that tamoxifen treatment causes a sudden decrease in the weight of the pregnant mother rats after the 7th day of gestation and that is accompanied by the high abortion rates and high percentage of resorbed fetuses compared to the control group animals. The fetuses of the treated mothers were characterized by growth retardation which is known by the decrease in the length and weight of the fetuses. There were an incre