Rapid Translocation Frequency Analysis in Humans Decades after Exposure to Ionizing Radiation

Abstract

This paper presents an analysis of the utility of fluorescence in situ hybridization (FISH) with whole-chromosome probes for measurement of the genomic frequency of translocations found in the peripheral blood of individuals exposed to ionizing radiation. First, we derive the equation: Fp = 2.05fp(1-fp)FG, relating the translocation frequency, Fp, measured using FISH to the genomic translocation frequency, FG, where fp is the fraction of the genome covered by the composite probe. We demonstrate the validity of this equation by showing that: (a) translocation detection efficiency predicted by the equation is consistent with experimental data as fp is changed; (b) translocation frequency dose-response curves measured in vitro using FISH agree well with dicentric frequency dose-response curves measured in vitro using conventional cytogenetic procedures; and (c) the genomic translocation frequencies estimated from FISH measurements for 20 Hiroshima A-bomb survivors and four workers exposed to ionizing radiation during the Y-12 criticality accident are approximately the same as the translocation frequencies measured using G-banding. We also show that translocation frequency dose response curves estimated using FISH are similar for Hiroshima A-bomb survivors and for first division lymphocytes irradiated in vitro. We conclude with a discussion of the potential utility of translocation frequency analysis for assessment of the level of acute radiation exposure independent of the time between analysis and exposure.

Effects of Ionising Radiation on Micronucleus Formation and Chromosomal Aberrations in Chinese Radiation Workers

“…A total of 100 lymphocytes were counted in each case, and the results were confirmed by two observers. Results were converted to full genome equivalence based on the formula: Fp ¼ 2.05fp(1 2 fp)FG (20) , where Fp is the CA rate detected by FISH (cell number of aberrations/100), fp is the target chromosome/full genome and FG is the CA rate of a full genome. The results were expressed as percentage.…”

Is FISH painting an appropriate biological marker for dose estimates of suspected accidental radiation overexposure? A review of cases investigated in France from 1995 to 1996.

“…Cells containing visible EC were scored separately and not included in the total data. To compare the yields of stable chromosome aberrations with those of the unstable aberrations, all observed frequencies were genomic estimated using the formula of Lucas et al (6,7). So a full genome equivalent cell number (cell equivalent) was calculated and the corresponding genomic estimated translocation number was termed (TR+ TT)eq.…”

“…The data obtained by the analysis of only a few chromosomes (the painted ones) generally are scaled up to full genomic frequency by assuming a random distribution of break points. FISH painting, therefore, provides easy identification and classification of radiation-induced chromosome aberrations (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

Science and engineering research semester internship, Fall 1996, abstracts and research papers

“…Only apparently simple translocations (AST'S) were used to calculate F-ratios . The translocation frequency measured by FISH was scaled to full genome equivalents using the Lucas et al formula (Lucas et al 1992). In brief, the formula relates the translocation frequency measured by FISH, FP, to the genomic translocation frequencies, FG, through the fraction of the genome covered by the probes, fp, as follows:…”

“…For Identification and scoring of translocations using FISH employed the methods of Lucas et al (1992). Only reciprocal translocations were used in determining the translocation frequency.…”