Prevention of radiation-induced mammary tumours in rats by combined use ofWR-2721 and tamoxifen

Purpose: This investigation evaluated the inhibitory effect of S-2-(3-amino propylamino)-ethylphosphorothioic acid (WR-2721) against the initiation of mammary tumourigenesis by irradiation, and the antipromotion activity of ta moxifen in the development of radiation-initiated mammary tumours. Materials and methods: Lactating rats were injected with WR-2721 and then i rradiated with gamma-rays (1.5 Gy) at day 21 of lactation. The rats were di vided into three groups 1 month after irradiation and were implanted with a pellet either of cholesterol as an inert control, diethylstilbestrol (DES) as a tumour-promoting agent, or DES combined with tamoxifen. For the contr ol experiments, non-irradiated and irradiated rats receiving saline instead of WR-2721 were treated with a pellet by the same procedures. Results: The highest incidence (85%) for tumourigenesis of mammary glands w as observed in the irradiated rats that had been previously injected with s aline following treatment with DES Administration of WR-2721 prior to the i rradiation significantly decreased the incidence of mammary tumours to 52.2 %. The treatment with DES pellets combined with tamoxifen in the irradiated rats previously injected with saline also markedly suppressed the incidenc e of mammary rumours even further to 4.4%. Also, the development of mammary rumours was completely prevented in the rats treated with WR-2721 prior to irradiation and then implanted with DES pellets combined with tamoxifen. Conclusions: These results suggest that the administration of WR-2721 prior to irradiation has an inhibitory effect on the initiation phase, resulting in a partial reduction of mammary tumour development, and that the combina tion of WR-2721 at the initiation phase with tamoxifen at the promotion pha se is quite effective in preventing mammary tumourigenesis induced by radia tion.