Fred W. Bruenger

Eye tumors and other lesions among beagles given 90Sr or 226Ra.

Analysis of eye tumors and other eye lesions among beagles given either 90Sr or 226Ra, and among control animals, indicated that intraocular tumors in excess of the rate for our control animals were not associated with radiation from incorporated 90Sr + 90Y. It is unequivocal that eye melanomas were produced by injected 226Ra. Intraocular neoplasia, hyperplasia, hyperpigmentation, and melanosis in the eye all occurred in our control beagles given no radioactivity; however, tumor experience as currently reported for different beagle colonies may not be directly comparable because of differing rates of discovery, nonuniform nomenclature, and varying criteria for classification of lesions with their discordant interpretation by different pathologists.

Comparisons of the Skeletal Locations of Putative Plutonium-Induced Osteosarcomas in Humans with those in Beagle Dogs and with Naturally Occurring Tumors in both Species

Abstract Miller, S. C., Lloyd, R. D., Bruenger, F. W., Krahenbuhl, M. P. and Romanov, S. A. Comparisons of the Skeletal Locations of Putative Plutonium-Induced Osteosarcomas in Humans with those in Beagle Dogs and with Naturally Occurring Tumors in both Species. Radiat. Res. 160, 517–523 (2003). Osteosarcomas occur from exposures to bone-seeking, α-particle-emitting isotopes, particularly plutonium. The skeletal distribution of putative 239Pu-induced osteosarcomas reported in Mayak Metallurgical and Radiochemical Plutonium Plant workers is compared with those observed in canine studies, and these are compared with distributions of naturally occurring osteosarcomas in both species. In the Mayak workers, 29% and 71% of the osteosarcomas were in the peripheral and central skeleton, respectively, with the spine having the most tumors (36%). An almost identical distribution of plutonium-induced osteosarcomas was reported for dogs injected with 239Pu as young adults. This distribution of osteosarcomas is quite different from the distributions of naturally occurring osteosarcomas for both species. In the Cooperative Osteosarcoma Study Group in humans (1,736 osteosarcomas from all ages), over 91% of the tumors occurred in the peripheral skeleton. In the Mayo Clinic group of older individuals (>40 years old), over 60% of the osteosarcomas appeared in the peripheral skeleton. The distribution of naturally occurring osteosarcomas in the canine is similar to that in the adult human. The similarities of the distributions of plutonium-associated osteosarcomas in the Mayak workers with those found in experimental studies suggest that many of the reported osteosarcomas may have been associated with plutonium exposures. These results also support the experimental paradigm that plutonium osteosarcomas have a preference for well vascularized cancellous bone sites. These sites have a greater initial deposition of plutonium, but also greater turnover due to elevated bone remodeling rates.

Distribution of skeletal malignancies in beagles injected with 239Pu citrate

The distribution of skeletal malignancies among our beagles injected with 239Pu as young adults roughly seems to follow the distribution of skeletal mass and skeletal 239Pu. These findings are similar to those we reported previously for a group of dogs given 26Ra. Although there were differences in tumor distribution between the animals given 226Ra and those given 239Pu, most of them were not statistically significant; however, the radium dogs seemed to show a greater sensitivity to bone tumor origin in the tibia, while there may have been a tendency among the plutonium dogs toward increased relative sensitivity in the scapula, lumbar vertebrae, sacrum, and ribs. In contrast, the most common site for the formation of naturally-occurring bone malignancy in the dog is the distal radius. Perhaps there were too few tumors and too few dogs to establish statistical significance. A correlation between tumor location and at least two anatomical-physiological factors in the skeleton indicated that these two factors (site-specific bone turnover rate and percent of red marrow at the site, which is correlated with vascularity) may influence the appearance of malignancies both individually and in combination. Except for the femur, there appeared to be no difference between the relative distribution of skeletal malignancies of low-level (30 Bq-2 Bq kg-1 injected) and high-level (3-122 kBq kg-1) dogs. Distribution of bone tumors between the axial and appendicular skeleton was 50% vs. 50% for 239Pu (42 and 42), but it was 39% axial vs. 61% appendicular (22 and 35, respectively) for dogs given 226Ra. This difference was not significant (p > 0.2).

Molecular structure and biological and pharmacological properties of 3-hydroxy-2-methyl-1-(β-D-ribofuranosyl or pyranosyl)-4-pyridinone: potential iron overload drugs for oral administration

Replacing alkyl groups by sugar moieties at N-1 position of 3-hydroxy-2-methyl-4-pyridinone did not affect the geometry of the iron chelating sites but increased the hydrophilic nature. The formation of a polymer cluster through the intermolecular hydrogen bonds was also revealed by X-ray crystal structure analysis for the first time in all known 3-hydroxy-4-pyridinone crystal structures. Iron removal from ferritin by the title compounds was more efficient than with DFO.

Dependency of Chelation Efficacy upon Time after First DTPA Injection

Fourteen young adult beagles were given an intravenous injection of either

Effectiveness of DTPA treatments following the injection of particulate plutonium.

{}^{241}{\rm Am}({\rm III})

Acyclonucleoside Iron Chelators of 1‐(2‐Hydroxyethoxy)methyl‐2‐alkyl‐3‐hydroxy‐4‐pyridinones: Potential Oral Iron Chelation Therapeutics

citrate or

A new linear polymer chain iron complex; synthesis, crystal and molecular structural characterization of catena-μ-acetato-[NN′-ethylenebis(salicylaldiminato)]iron(III)

{}^{239}{\rm Pu}({\rm IV})

Bone tumor location in dogs given skeletal irradiation by 239Pu or 226Ra

citrate (labeled with239 Pu) followed by a single intravenous injection of Ca-DTPA after an interval of 1 min, 6 min, 30 min, 150 min, 8 hr, 1 day, or 3 days. Animals were sacrificed 7 days after DTPA injection. Retention of241 Am at death was influenced strongly by early treatment. Dogs given Ca-DTPA at 1, 6, and 30 min retained about 3, 10, and 29%, respectively, of the injected241 Am, while the animal treated at 150 min retained 45%. Beagles given241 Am and then DTPA at 8 hr, 1 day, and 3 days, retained 58, 73, and 72%, respectively. For241 Am contamination, the first DTPA treatment should be given as soon as possible. Total-body retention of

Soft tissue tumors induced by monomeric 239Pu

{}^{239+237}{\rm Pu}