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

Purpose : This investigation evaluated the inhibitory effect of S-2- (3-aminopropylamino)-ethylphosphorothioic acid (WR-2721) against the initiation of mammary tumourigenesis by irradiation, and the antipromotion activity of tamoxifen in the development of radiation-initiated mammary tumours. Materials and methods : Lactating rats were injected with WR-2721 and then irradiated with γ-rays (1.5 Gy) at day 21 of lactation. The rats were divided 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 control 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 was observed in the irradiated rats that had been previously injected with saline following treatment with DES Administration of WR-2721 prior to the irradiation 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 incidence of mammary tumours even further to 4.4%. Also, the development of mammary tumours 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 WR2721 prior to irradiation has an inhibitory effect on the initiation phase, resulting in a partial reduction of mammary tumour development, and that the combination of WR-2721 at the initiation phase with tamoxifen at the promotion phase is quite effective in preventing mammary tumourigenesis induced by radiation.