CUMULATIVE GENETIC-DAMAGE IN HEMATOPOIETIC STEM-CELLS IN A PATIENT WITH A 40-YEAR EXPOSURE TO ALPHA-PARTICLES EMITTED BY THORIUM-DIOXIDE

Thorotrast, a colloidal suspension of the long-lived radionuclide, tho rium-232, was widely used as a radiographic contrast medium far severa l decades. Due to the poor excretion of the sol, however, Thorotrast w ould deposit in the liver, bone marrow and other tissue, and patients would receive alpha-particle irradiation for life. To gauge the cumula tive genetic damage to hematopoietic stem cells due to chronic exposur e to alpha particles, we conducted a multi-end-point evaluation in a 7 2-year-old man who had been administered a 32-ml bolus of Thorotrast d uring cerebral angiography performed over 40 years ago in 1950. Periph eral T lymphocytes were cultured to quantify the frequencies and cellu lar distributions of asymmetrical and symmetrical types of chromosome aberrations in first-division metaphases and micronuclei in cytokinesi s-arrested interphase II cells. Aberrations were scored using classica l chromosome group analysis methods and chromosome painting techniques . Assays of glycophorin-A (GPA) mutations in red blood cells were also performed to obtain a relative measurement of damage sustained by the erythroid stem cell population. Results revealed that approximately 3 0% of the lymphocytes in this patient contained one or more chromosome aberrations, the majority of which were of the ''stable'' type. About one-third of the lymphocytes with chromosome damage carried multiple aberrations, suggesting that significant numbers of stem cells survive exposures to alpha-particle radiation that induce complex genomic alt erations. Increased frequencies of GPA mutations were observed, demons trating that genomic damage is also induced in erythroid progenitors. The numbers of micronuclei in lymphocytes were only moderately increas ed compared to expected values for persons of comparable age, and thus this end point was not useful for quantifying exposure level. Despite the relatively severe burden of somatic cell damage induced by 40 yea rs of internal cr-particle irradiation, the patient remains surprising ly free of any serious illness. (C) 1997 by Radiation Research Society .