Pathological evaluation of WR-151327 administered orally in irradiated and non-irradiated male mice

Studies were made on the radioprotective and toxic effects of orally administered WR-151327 in male CD2F1 mice. The lowest dose of orally administered drug permitting probit analysis of data was 450 mg per kg. The calculated radioprotective dose reduction factors (DRF) at 450 mg per kg and 900 mg per kg of body weight (BW) WR-151327 were 1.2 and 1.3, respectfully. Pathological examination at 8, 30 or 90 days post administration of 100, 450, or 900 mg per kg of the drug demonstrated that the major target organ for orally dosed mice was the testes. There was a decrease in the number of cells in the germinal cell layers of testes from animals administered 450 mg per kg WR-151327 or 10 Gy whole body irradiation after eight days. Moreover, there was a dramatic reduction in the germinal cells in mice seminiferous tubules treated with a combination of 450 mg per kg WR-151327 plus 10 Gy radiation after eight days.