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

Elizabeth A Platz, J. K. Wiencke, K. T. Kelsey, M. L. Janower, D. Schottenfeld, L. B. Travis, M. B. Goldman

Research output: Contribution to journalArticle

Abstract

Purpose: Patients injected with thorotrast, a radiologic contrast medium used from the 1920s to early 1950s, received chronic internal exposure to thorium-232, an α-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 phosphoribosltransferase (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. Materials and methods: 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. Results: 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. Conclusion: Noting the limitations of small samples, long-term thorotrast survivors were observed to be at an increased risk for genetic damage.

Original languageEnglish (US)
Pages (from-to)955-961
Number of pages7
JournalInternational Journal of Radiation Biology
Volume76
Issue number7
StatePublished - 2000

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Thorium Dioxide
hypoxanthine
Hypoxanthine
chromosome aberrations
Aberrations
Chromosome Aberrations
Survivors
aberration
Contrast media
mutants
Contrast Media
Blood
Thorium
damage
blood
Lymphocytes
Metaphase
Liver Neoplasms
thorium
Epidemiologic Studies

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Nuclear Energy and Engineering
  • Radiation

Cite this

Platz, E. A., Wiencke, J. K., Kelsey, K. T., Janower, M. L., Schottenfeld, D., Travis, L. B., & Goldman, M. B. (2000). Chromosomal aberrations and hprt mutant frequencies in long-term American thorotrast survivors. International Journal of Radiation Biology, 76(7), 955-961.

Chromosomal aberrations and hprt mutant frequencies in long-term American thorotrast survivors. / Platz, Elizabeth A; Wiencke, J. K.; Kelsey, K. T.; Janower, M. L.; Schottenfeld, D.; Travis, L. B.; Goldman, M. B.

In: International Journal of Radiation Biology, Vol. 76, No. 7, 2000, p. 955-961.

Research output: Contribution to journalArticle

Platz, EA, Wiencke, JK, Kelsey, KT, Janower, ML, Schottenfeld, D, Travis, LB & Goldman, MB 2000, 'Chromosomal aberrations and hprt mutant frequencies in long-term American thorotrast survivors', International Journal of Radiation Biology, vol. 76, no. 7, pp. 955-961.
Platz, Elizabeth A ; Wiencke, J. K. ; Kelsey, K. T. ; Janower, M. L. ; Schottenfeld, D. ; Travis, L. B. ; Goldman, M. B. / Chromosomal aberrations and hprt mutant frequencies in long-term American thorotrast survivors. In: International Journal of Radiation Biology. 2000 ; Vol. 76, No. 7. pp. 955-961.
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AU - Platz, Elizabeth A

AU - Wiencke, J. K.

AU - Kelsey, K. T.

AU - Janower, M. L.

AU - Schottenfeld, D.

AU - Travis, L. B.

AU - Goldman, M. B.

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N2 - Purpose: Patients injected with thorotrast, a radiologic contrast medium used from the 1920s to early 1950s, received chronic internal exposure to thorium-232, an α-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 phosphoribosltransferase (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. Materials and methods: 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. Results: 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. Conclusion: Noting the limitations of small samples, long-term thorotrast survivors were observed to be at an increased risk for genetic damage.

AB - Purpose: Patients injected with thorotrast, a radiologic contrast medium used from the 1920s to early 1950s, received chronic internal exposure to thorium-232, an α-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 phosphoribosltransferase (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. Materials and methods: 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. Results: 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. Conclusion: Noting the limitations of small samples, long-term thorotrast survivors were observed to be at an increased risk for genetic damage.

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