ANTICARCINOGENIC ACTIVITY OF SIMVASTATIN DURING THE PROMOTION PHASE OF RADIATION-INDUCED MAMMARY TUMORIGENESIS OF RATS

Pregnant Wistar-MS rats received whole body irradiation with 2.6 Gy ga mma-rays from a Co-60 source at day 20 of pregnancy. Control rats were fed a basal diet and were implanted with a diethylstilbestrol (DES) p ellet at 30 days after weaning. In the experimental group, rats were f ed a diet containing simvastatin immediately after weaning and receive d a DES pellet at 30 days after weaning. A high incidence of total mam mary tumours was observed in the rats fed the control diet and treated with DES for 1 year. The administration of dietary simvastatin togeth er with DES treatment significantly decreased the incidence of mammary tumours. The development of adenocarcinoma in the control rats was si gnificantly higher than that in the rats fed the simvastatin diet, Aft er the administration of simvastatin to the experimental group for 1 y ear, the serum estradiol-17 beta concentration in these rats was marke dly reduced, but that of prolactin was not. No significant difference was seen in the development of the mammary glands between rats fed the control diet and those fed the simvastatin diet by whole mount observ ations. Simvastatin feeding produced an increased development of ER(-) PgR(-) tumours and a reduced incidence of ER+ PgR(+) tumours. These fi ndings suggest that simvastatin has a potent preventive activity durin g the DES-dependent promotion/progression phase of radiation-induced m ammary tumorigenesis.