Primary liver tumors in beagle dogs exposed by inhalation to aerosols of plutonium-238 dioxide

Abstract

Primary liver tumors developed in Beagle dogs exposed by inhalation to aerosols of 238PuO2. Initial deposition of 238PuO2 in the respiratory tract was followed by translocation of a portion of the 238Pu to the liver and skeleton, which resulted in a large dose commitment and tumor risk to all three tissues. In a population of 144 dogs exposed to 238PuO2, 112 dogs died or were killed 4000 days after 238Pu exposure, 100 dogs had osteosarcoma, and 28 dogs had lung cancers. At increasing times after exposure, however, liver lesions have become more pronounced. Ten primary liver tumors in nine animals were diagnosed in the dogs dying before 4000 days after exposure. An additional five primary liver tumors in three dogs occurred in 9 animals killed after 4000 days after exposure. The majority of these tumors have been fibrosarcomas. The liver tumors were usually not the cause of death, and rarely metastasized. The occurrence of liver tumors in this study indicates that 238Pu is an effective hepatic carcinogen. Liver carcinogenesis is assuming an increasing importance in this study at late times after inhalation exposure. These results suggest that the liver may be an important organ at risk for the development of neoplasia in humans at time periods long after inhalation of 238Pu.