Chromosomal aberrations and hprt mutant frequencies in long-term American thorotrast survivors

Purpose: Patients injected with thorotrast, a radiologic contrast medium us ed from the 1920s to early 1950s, received chronic internal exposure to tho rium-232, an alpha-emitter. Epidemiologic studies have observed markedly el evated risks of death from hepatic and hematologic cancers and extensive ch romosomal damage among these patients. Few investigations have correlated m ultiple measures of genetic damage to determine whether these have independ ent induction kinetics. The distribution of chromosomal aberrations (CA) an d mutant frequencies (MF) at the hypoxanthine phosphoribosyltransferase (hp rt) locus was evaluated in eight long-term thorotrast survivors (mean expos ure time = 47.4 years) and five individuals who received a nonradioactive c ontrast medium during the same era. Materials and methods: Peripheral blood lymphocytes were harvested from who le blood, CA were scored in 500 complete metaphases and a clonal assay was used to determine hprt MF. Symmetrical aberrations were not evaluated. Diff erences in frequencies and correlations between endpoints were assessed usi ng nonparametric methods. Results: Thorotrast-exposed individuals differed from the comparison group in total number of multicentrics and centric and acentric rings (per 500 ce lls [median, mean +/- sd]: 11, 18.3 +/- 23.1 vs 2, 2.4 +/- 1.1, p=0.04). Th ere was no difference between the groups on hprt MF (12.6, 15.9 +/- 13.5 vs 16.6, 14.0 +/- 8.8[ x 10(-6)]; p = 1.0). Among the exposed, hprt MF was mo derately correlated with the frequency of asymmetrical chromosomal aberrati ons, although the association was not statistically significant. Conclusion: Noting the limitations of small samples, long-term thorotrast s urvivors were observed to be at an increased risk for genetic damage.