Recent results of the German Thorotrast study--statistical evaluation of animal experiments with regard to the nonradiation effects in human thorotrastosis.
Our first long-term animal experiment made use of 1920 female Wistar rats divided into 20 groups of 96 animals each. These were injected at 12 weeks of age with different volumes and different dosages of Thorotrast which was enriched with 230Th to enhance the alpha-energy emission rate. The purpose of the study was to evaluate the effects due to the colloidal substance and the radiation. In the main experiment, 12 groups of rats were injected intravenously with 60, 120 and 300 microliters Thorotrast. 230Th was added to some Thorotrast preparations so that the total alpha-energy emission rate varied by factors of 1, 2, 5 and 10 relative to normal Thorotrast. Two groups were injected with 12 and 60 microliters of 50-fold enriched Thorotrast. One group was given 600 microliters of normal Thorotrast. In addition, we had 5 control groups, 1 NaCl and 4 Dextrin groups. The latter were injected with 60, 120, 300 or 600 microliters of Dextrin. The first animals died 8 months after injection, and the last 11 animals were killed 41 months after starting the experiment. The number of animals that developed a hepatic or splenic tumor increased by a factor of 10 in the highest dose-rate groups compared to controls. Our results demonstrated a linear correlation between the dose-rate and the number of primary hepatic and splenic tumors. It appeared that the volume of injected Thorotrast, by itself, had little influence on the number of tumors. However, at a constant dose-rate of 10, a 50-fold increase in the volume of Thorotrast (12-600 microliters) decreased the minimal tumor-appearance time by about 250 days.
D000818:Animals; D003102:Colloids; D003287:Contrast Media / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005860:Germany, West; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000401:mortality; D009374:Neoplasms, Experimental / Q000209:etiology / Q000401:mortality; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000401:mortality; D051381:Rats; D011919:Rats, Inbred Strains; D013160:Splenic Neoplasms / Q000209:etiology / Q000401:mortality; D013911:Thorium Dioxide / Q000009:adverse effects*
D003102:Colloids; D003287:Contrast Media; D013911:Thorium Dioxide