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

Osteosarcomas occur from exposures to bone-seeking, alpha-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.

Quantitative Plutonium Microdistribution in Bone Tissue of Vertebra From a Mayak Worker

“…Plutonium is initially deposited on bone surfaces but becomes buried and redistributed with time (Miller et al 2003). Thus the heavy surface concentrations of 239 Pu in the NIAR from the worker would suggest a more recent deposition.…”

“…The sample had been stored in neutral formalin for 12 years. The vertebra was selected because the vertebral column is a site with a higher propensity for plutonium-induced sarcomas in experimental animals (Miller et al 1986; Lloyd et al 1994) and humans (Miller 2002; Miller et al 2003). Additionally, the vertebral bodies have a greater content of plutonium per unit bone mass than most other bones (Kathren et al 1987).…”

“…Epidemiological studies of plutonium personnel cohort show the presence of a reliable correlation between radiation levels from incorporated plutonium and the risk of skeletal malignant tumors (Koshurnikova et al 2000). Furthermore, these plutonium-induced skeletal tumors tend to appear at skeletal sites that differ from naturally occurring tumors (Miller et al 2003). Other radionuclides that deposit in bone are also associated with skeletal cancers and include 224 Ra, 226 Ra, 228 Ra, 228 Th, 249 Cf, and 252 Cf (Lloyd et al1994).…”

Evaluation of optimal water fluoridation on the incidence and skeletal distribution of naturally arising osteosarcoma in pet dogs

“…Previous carcinogenic studies using radioactive isotopes or chemical carcinogens have been found to induce appendicular tumours in rodents, 4 however, there is a shift towards axial lesions in both humans and dogs for plutonium-induced OSA. 27 While the 'diffusion effect' may still occur to some extent, pet dogs are generally less likely to be exposed to commercially available bottled water or beverages that could impact municipal water and overall fluoride consumption. Lastly, because dogs are not prone to dental caries, they are not exposed to fluoride-containing dental products that can significantly contribute to total fluoride exposure in young children.…”

Lung, Liver and Bone Cancer Mortality After Plutonium Exposure in Beagle Dogs and Nuclear Workers

“…Epidemiologic studies have shown the risk of cancer incidence and mortality among MPA workers to be significantly related to both external and internal dose (Gilbert et al 2000(Gilbert et al , 2004Koshurnikova et al 1996;Shilnikova et al 2003;Tokarskaya et al 1995). Plutonium exposure has been associated with cancers of the lung, liver and bone, the sites of plutonium accumulation; further, increased cancer incidence and mortality were significantly associated with increased plutonium exposure (Gilbert et al 2000;Jacob et al 2007;Khokhryakov et al 2002;Kreisheimer et al 2000Kreisheimer et al , 2003Leggett et al 2005;Miller et al 2003;Sokolnikov et al 2008).…”