Tissue distribution of Thorotrast and role of internal irradiation in carcinogenesis

Carcinogenesis in Thorotrastosis has been assumed due to direct bombardment by α-particle with high linear energy transfer during decay of 232Th. To revisit the mechanism of carcinogenesis by Thorotrast (THR), we examined the tissue distribution of THR granules and two-dimensional distribution of radioactivity in the organs of Thorotrastosis patients and studied their spatial relationship to histopathological changes. The high radioactivity in the patients' organ was predominantly derived from decay of Thorium series and showed unique distribution, while the far lower natural radioactivity was mainly from Uranium series decay and fairly evenly distributed. It was found that a large majority of THR granules were phagocytized by macrophages and were embedded in extensive fibrosis. Cancer was rarely in the center of THR deposition but rather at a distance from the deposits. These observations may indicate that the predominant feature of THR deposition is the tissue damage by direct hit of α-particles and subsequent fibrosis. The effect of THR resembles action of toxic chemical agents, as several authors have pointed out. We therefore assume that carcinogenesis in Thorotrastosis is a combination of events, such as regeneration of liver tissue after radiation damage, emission of secondary electrons, ionization of the surrounding tissue, and β- or γ-ray from daughter nuclei of Thorium (Th). In this context, the role of α-particle is important but more intriguing.