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

Purpose: To reduce the long-term toxicity of 239Pu in rats by lifetime drinking of ZnDTPA solution and to investigate possible side-effects of the drug.

Materials and methods: Male Sprague-Dawley rats received a single injection of 239Pu citrate, alone or plus oral ZnDTPA. Additional groups were administered only ZnDTPA. Late tissue changes were evaluated by post-mortem examination, X-rays and histologically.

Results: The incidence of rat bearing osteosarcoma decreased after treatment to 35% as compared with 53% in untreated controls. The proportional incidence of osteosarcomas was reduced after ZnDTPA by more than the corresponding removal of 239Pu. Unexpectedly in the male rat, mammary tumours, mostly malignant, developed in 20% of rats that received 239Pu as compared with 0.5% in the untreated controls. After a lifetime drinking solely 3 x 10(-3) M ZnDTPA the incidence of diffuse glomerulosclerosis reached 29% as compared with 10% in controls.

Conclusions: In rat, protracted oral administration of ZnDTPA reduced the incidence of osteosarcomas after injection of 239Pu, even if treatment started 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-239Pu. An increased incidence of diffuse glomerulosclerosis was observed as a side effect of oral ZnDTPA only when given continuously, alone and in high amounts.