The beagle: an appropriate experimental animal for extrapolating the organ distribution pattern of Th in humans.

The concentrations and the organ distribution patterns of 228Th, 230Th and 232Th in two 9-y-old dogs of our beagle colony were determined. The dogs were exposed only to background environmental levels of Th isotopes through ingestion (food and water) and inhalation as are humans. The organ distribution patterns of the isotopes in the beagles were compared to the organ distribution patterns in humans to determine if it is appropriate to extrapolate the beagle organ burden data to humans. Among soft tissues, only the lungs, lymph nodes, kidney and liver, and skeleton contained measurable amounts of Th isotopes. The organ distribution pattern of Th isotopes in humans and dog are similar, the majority of Th being in the skeleton of both species. The average skeletal concentrations of 228Th in dogs were 30 to 40 times higher than the average skeletal concentrations of the parent 232Th, whereas the concentration of 228Th in human skeleton was only four to five times higher than 232Th. This suggests that dogs have a higher intake of 228Ra through food than humans. There is a similar trend in the accumulations of 232Th, 230Th and 228Th in the lungs of dog and humans. The percentages of 232Th, 230Th and 228Th in human lungs are 26, 9.7 and 4.8, respectively, compared to 4.2, 2.6 and 0.48, respectively, in dog lungs. The larger percentages of Th isotopes in human lungs may be due simply to the longer life span of humans. If the burdens of Th isotopes in human lungs are normalized to an exposure time of 9.2 y (mean age of dogs at the time of sacrifice), the percent burden of 232Th, 230Th and 228Th in human lungs are estimated to be 3.6, 1.3 and 0.66, respectively. These results suggest that the beagle may be an appropriate experimental animal for extrapolating the organ distribution pattern of Th in humans.

Isolation of labeled triiodothyronine from serum using affinity chromatography: application to the extimation of the peripheral T4 to T3 conversion in rats.

A method for the isolation of small quantities of labeled 3,5,3' -triiodothyronine (T3) from serum or thyroid extracts is described. Conjugates of rabbit anti-T3 antibody to Sepharose 4B are incubated with 0.5 to 1 ml of human or rat serum at pH 8.6 for 1 hr. The tubes are centrifuged and washed with buffer followed by 6 M guanidine to remove nonspecifically bound labeled thyroxine (T4). The fraction of T3 and T4 bound to the Sepharose conjugate varies depending on the concentration of serum in the initial incubation tubes, the T3 and T4 content, and the specificity of the antiserum used. In a system that contains 0.5 ml of normal human serum, 1 ml of glycine-acetate buffer (pH 8.6), and 0.25 ml settled Sepharose-anti-T3 conjugate, the T3 to T4 binding ratio was generally 150-200, with up to as much as 50% of T3 bound to the pellet. The coefficient of variation of the method is less than 5%, and it may be performed in a matter of hours. There is no detectable conversion of T4 to T3 during the separation process. Using this technique, conversion of T4 to T3 was evaluated in euthyroid rats after injection of 125l-T4. Over the period of 36-72 hr after injection, a ratio of T3 to T4 of 0.74 +- 0.06 x 10-2 (mean +- SE) was present in the plasma. Using the calculated metabolic clearance rates for T3 and T4 in these animals, fractional conversion of T4 to T3 was estimated to be 27%, in good agreement with results obtained by other techniques. This method would appear to be of value for specific isolation of the small quantities of T3 produced from T4 after in vivo or in vitro T4 to T3 conversion.