A comparison of conventional metaphase analysis of Giemsa-stained chromosomes with multi-colour fluorescence in situ hybridization analysis to detect chromosome aberrations induced by daunomycin

Chromosome aberrations induced by daunomycin, a widely used positive control compound for in vitro cytogenetics assays, were identified by multi-colour fluorescence in situ hybridization with probes for chromosomes 1, 2 and 3. The frequency and distribution of aberration types were compared to conventional metaphase analysis of Giemsastained chromosomes from parallel human lymphocyte cultures. Multi-colour chromosome painting was a more sensitive method for detecting daunomycin-induced chromosome aberrations compared with conventional metaphase analysis because: (i) a higher level of statistical significance was achieved at low doses; and (ii) the increases in aberration frequencies compared with controls were greater. The majority of exchanges identified by Giemsastaining were unstable and were likely to lead to cell death. In contrast, those detected by FISH were mostly stable exchanges which may be transmitted to cell progeny. Multicolour FISH using whole chromosome probes may provide an elegant solution to the problem of identifying non-lethal, heritable exchange events. The benefit of this technique is the quantification of a cytogenetic endpoint directly associated with carcinogenesis.