GENETIC AND CYTOGENETIC MARKERS OF EXPOSURE TO HIGH-LINEAR ENERGY-TRANSFER RADIATION

It has been suggested that the more closely spaced, clustered DNA brea ks seen with high-LET radiations are more likely to result in chromoso me intrachanges than in chromosome interchanges. We determined whether analysis of the spectra of chromosome aberrations or Hprt gene mutati ons in CHO-K1 cells could detect a shift to more chromosome intrachang es and therefore distinguish exposure to high-LET radiation from expos ure 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 C HO-KI and xrs-5 cells exposed to Co-60 gamma rays or Bi-212 alpha part icles. Xrs-5 cells are a radiosensitive derivative of CHO-K1 cells tha t 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 fre quency of large interstitial deletions at the Hprt locus, determined b y multiplex polymerase chain reaction-based exon deletion analysis, wa s the same for both gamma-ray- and alpha-particle-exposed cells in eac h of the cell lines. Thus the F ratio can distinguish high-LET from lo w-LET radiations, and the end point is not influenced by differences i n the processing of DNA double-strand breaks. The analysis of the spec trum of Hprt mutations, however, appears unable to discriminate low LE T from high LET. (C) 1997 by Radiation Research Society.