Comparison of internal emitter radiobiology in animals and humans.

Investigations of radionuclide metabolism and effects in various mammalian species revealed important similarities between animals and humans and between some animal species. These include skeletal deposition of radium and radiostrontium in bone volume; deposition on bone surfaces of plutonium and other actinides; liver deposition of actinides; induction of skeletal or liver malignancies by these radionuclides; induction of tooth and jaw abnormalities; mammary cancer induction by radium in humans and in the beagle; depression of circulating cells in blood; and induction of bone fractures. There are also inter-species differences that may not have been noted if multiple species (including humans) had not been studied. Some of these are more rapid excretion of radium in humans compared with most other mammals; induction by radium of eye melanomas in animals but not humans; rapid loss of deposited plutonium from liver in many species of mice and rats but not in humans and dog; substantial sex-related differences in skeletal plutonium retention and bone sarcoma induction in mice but not in humans or dog; and induction of head sinus carcinomas by 226Ra in humans but not the beagle. Leukemia and other related neoplasms were not induced in radionuclide-injected lifespan dogs in excess of the occurrence in control animals. Much of our current understanding of skeletal biology and radionuclide behavior in mammals was derived from this and related projects. The primary goal of the Utah experiment of estimating toxicities of bone-seeking radionuclides relative to radium has been accomplished. For 226Ra = 1.0, comparative toxicities (ratios) of a single injection for bone tumor induction in beagles were about 16 +/- 5 for monomeric 239Pu (32 +/- 10 for chronic exposure), 6 +/- 0.8 for 241Am, 8.5 +/- 2.3 for 228Th, 6 +/- 3 for 249Cf, 4 +/- 2 for 252Cf, 6 +/- 2 for 224Ra (16 +/- 5 for 50 weekly injections), 2 +/- 0.5 for 228Ra, and between 0.01 +/- 0.01 and 1.0 +/- 0.5 for 90Sr, depending on the dose-rate, with the lowest dose-rates approaching a ratio of zero. Corresponding ratios in mice for 226Ra = 1.0 were 16 +/- 4 for monomeric 239Pu, 5.4 +/- 2.0 for 224Ra (16 for 50 weekly injections), 4.9 +/- 1.4 for 241Am, 5.0 +/- 1.4 for 249Cf, 2.6 +/- 0.8 for 252Cf, 4.4 +/- 1.8 for 243,244Cm and about 1.0 for 90Sr at high doses, decreasing to near zero for low doses.