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 pai nting is usually extrapolated from the observed frequency of aberrations by correcting for the DNA content of the labelled chromosomes. This extrapola tion is based upon the assumption of random distribution of breakpoints fro m which aberrations are generated. However, the validity of this assumption has been widely questioned. While extensive investigations have been perfo rmed with ionizing radiation as chromosome breaking agent, little efforts h ave been done with chemical clastogens. In order to investigate interchromo somal differences in chemically-induced chromosome damage, we have used mul ticolour chromosome painting to analyse bleomycin-induced aberrations invol ving chromosomes 1 and 4, two chromosomes that differ in gene density. In a ddition, we have measured the effect of cytosine arabinoside upon the repai r of bleomycin-induced DNA damage in chromosomes 1 and 4. Our results show that these chromosomes are equally sensitive to the clastogenic effect of b leomycin with a similar linear dose-effect relationship. However, the high gene density chromosome 1 appeared to be more sensitive to repair inhibitio n by Ara-C than chromosome 4. This enhanced sensitivity to repair inhibitio n in chromosome I could be mediated by preferential repair of open chromati n and actively transcribed regions. (C) 1999 Elsevier Science B.V. All righ ts reserved.