Analysis of bleomycin- and cytosine arabinoside-induced chromosome aberrations involving chromosomes 1 and 4 by painting FISH

The genomic frequency of chromosomal aberrations obtained by chromosome painting is usually extrapolated from the observed frequency of aberrations by correcting for the DNA content of the labelled chromosomes. This extrapolation is based upon the assumption of random distribution of breakpoints from which aberrations are generated. However, the validity of this assumption has been widely questioned. While extensive investigations have been performed with ionizing radiation as chromosome breaking agent, little efforts have been done with chemical clastogens. In order to investigate interchromosomal differences in chemically-induced chromosome damage, we have used multicolour chromosome painting to analyse bleomycin-induced aberrations involving chromosomes 1 and 4, two chromosomes that differ in gene density. In addition, we have measured the effect of cytosine arabinoside upon the repair of bleomycin-induced DNA damage in chromosomes 1 and 4. Our results show that these chromosomes are equally sensitive to the clastogenic effect of bleomycin with a similar linear dose-effect relationship. However, the high gene density chromosome 1 appeared to be more sensitive to repair inhibition by Ara-C than chromosome 4. This enhanced sensitivity to repair inhibition in chromosome 1 could be mediated by preferential repair of open chromatin and actively transcribed regions.