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.
Khan
Fauzia
F
Department of Zoology, Aligarh Muslim University, Aligarh, India.
Sherwani
Asma Farhat
AF
Afzal
Mohammad
M
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004317:Doxorubicin / Q000633:toxicity*; D006801:Humans; D015255:Idarubicin / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced / Q000187:drug effects*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity; D059005:Topoisomerase II Inhibitors
D000903:Antibiotics, Antineoplastic; D009153:Mutagens; D059005:Topoisomerase II Inhibitors; D004317:Doxorubicin; D015255:Idarubicin