Genetic and cytogenetic markers of exposure to high-linear energy transfer radiation.
It has been suggested that the more closely spaced, clustered DNA breaks seen with high-LET radiations are more likely to result in chromosome intrachanges than in chromosome interchanges. We determined whether analysis of the spectra of chromosome aberrations or Hprt gene mutations in CHO-K1 cells could detect a shift to more chromosome intrachanges and therefore distinguish exposure to high-LET radiation from exposure to low-LET radiation, and whether alterations in the processing of DNA breaks would influence this process. Both the frequency and type of chromosome aberrations and Hprt gene mutations were determined in CHO-K1 and xrs-5 cells exposed to 60Co gamma rays or 212Bi alpha particles. Xrs-5 cells are a radiosensitive derivative of CHO-K1 cells that are defective in rejoining of DNA double-strand breaks. The ratio of dicentrics to centric rings (F ratio) was significantly lower in CHO-K1 and xrs-5 cells exposed to alpha particles, consistent with a shift to more chromosome intrachanges with higher LET. In contrast, the frequency of large interstitial deletions at the Hprt locus, determined by multiplex polymerase chain reaction-based exon deletion analysis, was the same for both gamma-ray- and alpha-particle-exposed cells in each of the cell lines. Thus the F ratio can distinguish high-LET from low-LET radiations, and the end point is not influenced by differences in the processing of DNA double-strand breaks. The analysis of the spectrum of Hprt mutations, however, appears unable to discriminate low LET from high LET.
Schwartz
J L
JL
Department of Radiation Oncology, University of Washington, Seattle 98195, USA.
Hsie
A W
AW
D000512:Alpha Particles; D000818:Animals; D015415:Biomarkers; D016466:CHO Cells; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000528:radiation effects*; D006224:Cricetinae; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D018499:Linear Energy Transfer; D011874:Radiometry
D015415:Biomarkers; D007041:Hypoxanthine Phosphoribosyltransferase