Genotoxic Effects of the Anti-Cancer Drug Doxorubicin (Dxr) in the Bone Marrow Cells of Swiss Albino Mice (Mus musculus)

Abstract

The antineoplastic chemotherapeutic agent doxorubicin (DXR) is probably the most utilized drug for treating many human cancers. In the current study we aimed to evaluate the genotoxic effects of doxorubicin Swiss mice bone marrow cells using the toxicological endpoints chromosomal aberrations, mitotic index and micronuclei formation. Twelve male animals, aged 6-8 weeks and weighing 24±2g were divided into four groups. One group served as control was intraperitoneally injected only with distilled water. The three remaining groups were injected intraperitoneally with single doses of doxorubicin (0.2, 0.4 and 0.8 mg/g body weight) for two consecutive days. 24 hours later, animals were anaesthetized and killed by cervical dislocation. Colchicine (0.05 %) was injected to animals 90 minutes before sacrifice. After sacrificing the animals, both femurs were dissected out and the bone marrow cells obtained. All treatments with doxorubicin caused an increased significance in the incidence of chromosomal aberrations (CA) and micronuclei formation in polychromatic erythrocytes (PCEs) cells. Meanwhile, there was a gradual repression in the mitotic index (MI) percentages of the treated groups compared to that of the control. Different types of chromosomal aberrations (structural and numerical) were induced as a result of doxorubicin treatments. These includes: gaps, breaks, fragments, rings, centric fusions (CF) and polyploidy. The mean percentages of total chromosomal aberrations increased from 3.33 ± 0.28 in the control group to 12.67 ± 2.42, 29.00 ± 4.27 and 38.67 ± 2.82 for doses 0.2, 0.4 and 0.8 mg/kg B.W. respectively. The numbers of micronucleated PCEs observed in mice cells treated with doxorubicin were increased from 4.67±0.48 for the control group to 7.00±1.02, 10.67±2.10 and 17.67 for the three doses respectively. Meanwhile, the PCE / (PCE+NCE) ratio calculated in treated animals were 0.85 ± 0.02, 0.63 ± 0.08 and 0.54 ± 0.10 compared to 0.94 ± 0.12 for the control. Our results indicated that doxorubicin has genotoxic as well as cytotoxic effects in mice bone marrow cells.