Morphine modulates doxorubicin-induced genomic instability with distinct effects in osteosarcoma and fibroblast cells

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ID: 324321
2026
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Abstract
Osteosarcoma is an aggressive malignant bone tumor that often requires chemotherapy with agents such as doxorubicin (Dox), which is known for its potent cytotoxic and genotoxic effects. To manage cancer-related pain, morphine is widely used due to its strong analgesic properties. The concurrent administration of these drugs in clinical practice might affect cancer therapy, since Dox is a well-established inducer of genomic instability, whereas the potential contribution of morphine to this process remains poorly understood. This study evaluated the cytotoxicity, genotoxicity, and chromosomal damage induced by morphine, both alone and in combination with Dox. Cytotoxicity was assessed in MG63 osteosarcoma cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Genotoxicity and chromosomal damage were evaluated in MG63 and non-tumor V79 fibroblast cells using the comet assay and the cytokinesis-block micronucleus (CBMN) assay. Morphine alone induced DNA damage in both MG63 and V79 cells in the comet assay and increased micronucleus frequency only in MG63 cells. In co-treatment, morphine significantly reduced Dox-induced DNA damage and chromosomal instability parameters in the CBMN assay in MG63 cells. Conversely, micronucleus frequency increased in co-treatment in V79 cells. Overall, morphine alone increased chromosomal damage in MG63 tumor cells but not in V79 non-tumor cells. However, in combination with Dox, morphine attenuated Dox-induced genomic instability in osteosarcoma cells while enhancing chromosomal damage in non-tumor fibroblasts. These findings suggest that morphine may differentially modulate the genomic effects of Dox, potentially impacting both antitumor efficacy and genomic stability in normal cells.
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Authors Jayne Torres de Sousa, Rafael Rodrigues Dihl, CRISTINA BRAUWERS KUBIAKI, Gumercindo Pimentel-Peralta, Juliana da Silva, Ivana Grivicich, Jaqueline Nascimento Picada
Journal mutation research/genetic toxicology and environmental mutagenesis
Year 2026
DOI
10.1093/mutage/geag028
URL
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