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


METHODS
Lactating rats were injected with WR-2721 and then irradiated with gamma-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 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 combination of WR-2721 at the initiation phase with tamoxifen at the promotion phase is quite effective in preventing mammary tumourigenesis induced by radiation.
Inano
H
H
First Research Group, National Institute of Radiological Sciences, Chiba-shi, Japan. inano@nirs.go.jp
Onoda
M
M
Suzuki
K
K
Kobayashi
H
H
Wakabayashi
K
K
D004999:Amifostine / Q000008:administration & dosage*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000209:etiology* / Q000517:prevention & control*; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000008:administration & dosage*
D018931:Antineoplastic Agents, Hormonal; D011837:Radiation-Protective Agents; D013629:Tamoxifen; D004999:Amifostine