A possible role by cadmium-induced metallothionein in radiation protection following gamma irradiation in rats
Smith, Steven Thomas
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Fisher strain F-344 rats, approximately seventy days of age, (+OR-)ten days, were used to determine what effect, if any, the metalloprotein, metallothionein, has on increasing the lethal dose of gamma radiation from a ('60)Co source. Production of metallothionein was induced utilizing single injections of 1 mg CdCl(,2) in water/kg of body weight. Ultrastructural examination of three selected cadmium-sensitive tissues, liver, kidney, and testes was performed to determine if the dosage of cadmium given would cause demonstrable damage. No pathological changes were noted in any of the tissues examined. This information was correlated with a lethality study, in which a group of 10 animals was given a single subcutaneous injection of 1 mg CdCl(,2)/kg body weight and observed for 30 days. No deaths were observed in this group of animals after 30 days. A determination of the level of induced metallothionein utilizing atomic absorption spectroscopy was made. There were approximately 3.50 x 10('-6) umoles of metallothionein/mg of liver, 1.11 x 10('-5) umoles/mg of kidney tissue, and 9.96 x 10('-6) umoles/mg of testes. A lethality study was performed on 3 groups of 10 animals each at 9, 9.5, and 10 Gy of gamma radiation from a ('60)Co source. This procedure was performed in order to demonstate an LD 50/30 dose of gamma radiation from a ('60)Co source. All animals in both the 9.5 Gy and 10 Gy groups died within 10 days. Fifty percent of the animals in the 9 Gy group died after 14 days, with no further deaths after 30 days. The 9 Gy level was then determined to be the LD 50/30 dose. To determine to what extent metallothionein affects the LD 50/30 of gamma radiation, a group of animals was first injected with 1 mg CdCl(,2)/kg body weight then allowed to synthesize metallothionein for 4 hours. Then the animals were divided into two subgroups which were then exposed to 0.5 Gy and 1 Gy above the LD 50/30 level of gamma radiation from a ('60)Co source. Fifty percent of the animals receiving 0.5 Gy above the LD 50/30 and ten percent of the animals receiving 1 Gy above the LD 50/30 level survived. Since CdCl(,2) induces metallothionein synthesis, this would seem to indicate that metallothionein could have a role in protecting the animals from the effects of radiation.