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

Patients injected with thorotrast, a radiologic contrast medium used from the 1920s to early 1950s, received chronic internal exposure to thorium-232, an alpha-emitter. Epidemiologic studies have observed markedly elevated risks of death from hepatic and hematologic cancers and extensive chromosomal damage among these patients. Few investigations have correlated multiple measures of genetic damage to determine whether these have independent induction kinetics. The distribution of chromosomal aberrations (CA) and mutant frequencies (MF) at the hypoxanthine phosphoribosyltransferase (hprt) locus was evaluated in eight long-term thorotrast survivors (mean exposure time=47.4 years) and five individuals who received a nonradioactive contrast medium during the same era.

Peripheral blood lymphocytes were harvested from whole blood, CA were scored in 500 complete metaphases and a clonal assay was used to determine hprt MF. Symmetrical aberrations were not evaluated. Differences in frequencies and correlations between endpoints were assessed using nonparametric methods.

Thorotrast-exposed individuals differed from the comparison group in total number of multicentrics and centric and acentric rings (per 500 cells [median, mean +/- sd]: 11, 18.3+/-23.1 vs 2, 2.4+/-1.1, p =0.04). There 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 moderately correlated with the frequency of asymmetrical chromosomal aberrations, although the association was not statistically significant.

Noting the limitations of small samples, long-term thorotrast survivors were observed to be at an increased risk for genetic damage.