Chromosomal aberration and micronucleus studies of two topoisomerase (II) targeting anthracyclines

Anthracycline antibiotics are widely used in cancer chemotherapy. Doxorubicin and Idarubicin, topoisomerase-targeting anthracyclines, were examined for their effect on chromosomal aberration and micronucleus induction in cultured human lymphocytes employing lymphocyte transformation test and cytokinesis-blocked micronucleus (CBMN) assay. A statistically significant dose-dependent increase in micronucleus frequency (p < 0.001) in binucleated cells was seen as well as a significant increase in chromosomal aberration frequency was also observed for both the drugs. A variety of aberrations were scored including terminal deletions, breaks, gaps, exchanges, fragment formation, ends rejoining, interstitial deletions etc. Nuclear division index was also calculated and showed a cell cycle delay towards higher doses. A number of necrotic and apoptotic cells were also observed at higher concentrations. This confirms the two drugs to be clastogenic and aneugenic.