Analysis for DNA-proportional Distribution of Radiation-induced Chromosome Aberrations in Various Triple Combinations of Human Chromosomes Using Fluorescence in Situ Hybridization

Abstract

Fluorescence in situ hybridization (FISH) with five cocktails of composite whole chromosome-specific DNA probes 1, 4, 12; 2, 7, 9; 2, 7, 9_dig; 3, 6, 10_dig and 8, 14 X_dig and a degenerate α-satellite pancentromeric DNA probe was used to examine in vitro radiation-induced symmetrical translocations and dicentrics in peripheral lymphocytes for a DNA-proportional distribution. For a discrimination between morphologically similar target chromosomes, chromosomes 9, 10 and X were labelled with digoxigenin (dig). Among the five combinations, significantly higher translocation frequencies than expected from the DNA content were found in 8, 14, X_dig, whereas for this combination no deviation became apparent for dicentrics. The chromosome-specific analysis showed that chromosome 2 was involved in fewer symmetrical translocations, whereas chromosomes 9, 10 and 12 were more frequently involved in dicentrics than predicted. Comparing the ratios of symmetrical translocations to dicentrics, an excess of symmetrical translocations was found for the combinations 1, 4, 12; 2, 7, 9_dig and 8, 14, X_dig and for the chromosomes 1, 4, 6, 7, 8 and X. Provided the present data can be confirmed in further experiments, the formula Ŷ_i = 2·05f_i(1 − f_i)F_G, relating the translocation or dicentric frequency measured by FISH to the respective genomic F_G (fi is the labelled genomic fraction) cannot be used to scale up to equal the full genome unless appropriate weighting factors are included.