CHEMOPREVENTION OF RADIATION-INDUCED MAMMARY-TUMORS IN RATS BY BEZAFIBRATE ADMINISTERED TOGETHER WITH DIETHYLSTILBESTROL AS A PROMOTER

Pregnant Wistar-MS strain rats were irradiated with 2.6 GS of gamma-ra ys at day 20 of pregnancy, Rats in the control group (n = 48) were the n implanted with a diethylstilbestrol (DES) pellet at 35 days after we aning, while being fed a control (MB-1) diet, The incidence of mammary tumors was 89.6% within 1 year, In the experimental group (n 22), a b ezafibrate (0.15%) diet was initiated immediately after weaning, and 3 5 days after weaning a DES pellet was implanted. Administration of die tary bezafibrate together with DES-implantation continued for a period of 1 year, at which time the experiment was terminated, The incidence (27.3%) of the mammary tumors in the bezafibrate-fed rats was less th an one-third of that in the control rats, Compared with the control gr oup, the number of mammary tumors per tumor-bearing rat in the bezafib rate-treated group was reduced, For clarification of the mechanism of the chemopreventive effects of bezafibrate, lipid and hormone concentr ations in serum were measured, Bezafibrate-fed rats showed a significa nt decrease in serum prolactin (56%) and triglyceride (63%) concentrat ions, and a significant increase in serum estradiol-17 beta (3.8-fold) , cholesterol ester (2.0-fold) and TSH (2.0-fold) concentrations in co mparison with the control rats, The bezafibrate diet inhibited the for mation of DES-induced pituitary tumors. However, the development of ma mmary glands in the bezafibrate-fed rats was stimulated more than that in the control rats treated with DES alone, The present results demon strate that bezafibrate is effective in preventing mammary tumors indu ced by radiation together with DES, possibly by reducing prolactin and triglyceride concentrations.