INDUCTION OF CHROMOSOMAL-ABERRATIONS (UNSTABLE AND STABLE) BY INHIBITORS OF TOPOISOMERASE-II, M-AMSA AND VP16, USING CONVENTIONAL GIEMSA STAINING AND CHROMOSOME PAINTING TECHNIQUES

Frequencies of symmetrical and asymmetrical exchange aberrations induc ed by two inhibitors of topoisomerase II, namely, 4'-(9-acridinylamino ) methanesulfon-m-anisidide (m-AMSA) and etoposide (VP16), were estima ted in human peripheral blood lymphocytes, The aberrations were scored using conventional Giemsa staining and fluorescence in situ hybridiza tion (FISH) techniques, using chromosome-specific DNA libraries, Stabl e aberrations (translocations) were detected using two cocktails of DN A libraries specific for three chromosomes, namely 1, 3 and X and 2, 4 and 8, representing similar to 40% of the whole human genome, The fre quencies of dicentrics and translocations increased in a dose-dependen t manner, however, m-AMSA was found to be a more potent inducer of chr omosomal aberrations in comparison with VP16 (at concentrations at whi ch comparable frequencies of aberrations were induced) by 20- to 30-fo ld, When corrected for DNA content of chromosomes in each cocktail, a higher frequency of translocations with the cocktail consisting of chr omosomes 2, 4 and 8 in comparison with 1, 3 and X was evident, The gen omic translocation frequency calculated from chromosome painting analy sis for m-AMSA exceeded that estimated for dicentrics by similar to 2- fold, However, for VP16 almost equal frequencies of both types of chro mosome exchange were found.