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 induced by two inhibitors of topoisomerase II, namely, 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA) and etoposide (VP16), were estimated in human peripheral blood lymphocytes. The aberrations were scored using conventional Giemsa staining and fluorescence in situ hybridization (FISH) techniques, using chromosome-specific DNA libraries. Stable aberrations (translocations) were detected using two cocktails of DNA libraries specific for three chromosomes, namely 1, 3 and X and 2, 4 and 8, representing approximately 40% of the whole human genome. The frequencies of dicentrics and translocations increased in a dose-dependent manner, however, m-AMSA was found to be a more potent inducer of chromosomal aberrations in comparison with VP16 (at concentrations at which comparable frequencies of aberrations were induced) by 20- to 30-fold. When corrected for DNA content of chromosomes in each cocktail, a higher frequency of translocations with the cocktail consisting of chromosomes 2, 4 and 8 in comparison with 1, 3 and X was evident. The genomic translocation frequency calculated from chromosome painting analysis for m-AMSA exceeded that estimated for dicentrics by approximately 2-fold. However, for VP16 almost equal frequencies of both types of chromosome exchange were found.
Mosesso
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P
Dipartimento di Agrobiologia e Agrochimica, Università degli studi della Tuscia, Viterbo, Italy.
Darroudi
F
F
van den Berg
M
M
Vermeulen
S
S
Palitti
F
F
Natarajan
A T
AT
D000677:Amsacrine / Q000494:pharmacology*; D001399:Azure Stains; D002869:Chromosome Aberrations / Q000235:genetics*; D002871:Chromosome Banding / Q000379:methods*; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D008297:Male; D013194:Staining and Labeling; D059005:Topoisomerase II Inhibitors; D014178:Translocation, Genetic / Q000187:drug effects
D001399:Azure Stains; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D005047:Etoposide