Mechanistic Divergence in Chemotherapy-Induced Genotoxicity: A Comparative in vivo Assessment of Different Antineoplastic Drug Classes in Murine Bone Marrow and Spleen

Afrah Thiab Hlail; Ali Faris Hassan; Nada Naji Al-Shawi

المؤلفون

Afrah Thiab Hlail Department of Pharmacognosy and Medicinal Plants, College of Pharmacy, University of Thi-qar, Nasiriyah 64001, Iraq https://orcid.org/0000-0001-9223-2850
Ali Faris Hassan Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq https://orcid.org/0009-0001-5650-1272
Nada Naji Al-Shawi Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq

الكلمات المفتاحية:

Antineoplastic agents، Chromosome aberrations، Genotoxicity، Micronucleus tests، Mitotic index

الملخص

Background: Cancer chemotherapeutic agents, while effective against malignant cells, can also damage rapidly dividing normal tissues such as the bone marrow, raising concern about their genotoxic potential. Objective: To compare the acute in vivo cytotoxic and genotoxic effects of four mechanistically distinct antineoplastic agents on the bone marrow and splenic cells of albino mice. Methods: Sixty albino mice were randomly allocated to five groups (n=12): a negative control receiving distilled water and four groups receiving a single intraperitoneal dose of cisplatin (12 mg/kg), methotrexate (20 mg/kg), doxorubicin (5 mg/kg), or cyclophosphamide (50 mg/kg). Twenty-four hours after treatment, bone marrow and spleen samples were evaluated for mitotic index (MI), total chromosomal aberrations (TCA), and micronucleus (MN) frequency. Results: All four agents significantly reduced MI and increased TCA and MN frequency in both tissues compared with the control (p<0.05). Methotrexate produced the smallest changes across all endpoints, whereas cyclophosphamide and cisplatin produced moderate, distinct effects. Doxorubicin caused the greatest reduction in MI and the highest TCA and MN frequencies. Conclusions: Genotoxicity ranked doxorubicin > cyclophosphamide > cisplatin > methotrexate, inversely reflecting the antiproliferative potency of these agents and paralleling the hematological toxicity observed clinically.

التنزيلات

بيانات التنزيل غير متوفرة بعد.

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