Effect of oral ZnDTPA on late effects of injected plutonium in rat

Purpose: To reduce the long-term toxicity of Pu-239 in rats by lifetime dri nking of ZnDTPA solution and to investigate possible side-effects of the dr ug. Materials and methods: Male Sprague-Dawley rats received a single injection of Pu-239 citrate, alone or plus oral ZnDTPA. Additional groups were admin istered only ZnDTPA. Late tissue changes were evaluated by post-mortem exam ination, X-rays and histologically. Results: The incidence of rat bearing osteosarcoma decreased after treatmen t to 35% as compared with 53% in untreated controls. The proportional incid ence of osteosarcomas was reduced after ZnDTPA by more than the correspondi ng removal of Pu-239. Unexpectedly in the male rat, mammary tumours, mostly malignant, developed in 20% of rats that received Pu-239 as compared with 0.5% in the untreated controls. After a lifetime drinking solely 3 x 10(-3) hr ZnDTPA the incidence of diffuse glomerulosclerosis reached 29% as compa red with 10% in controls. Conclusions: In rat, protracted oral administration of ZnDTPA reduced the i ncidence of osteosarcomas after injection of Pu-239, even if treatment star ted with a delay of 1 month. In the latter case, however, more soft tissue damage was found than after treatment beginning at 4 days post-Pu-239. An i ncreased incidence of diffuse glomerulosclerosis was observed as a side eff ect of oral ZnDTPA only when given continuously, alone and in high amounts.