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The clastogenicity of morphine sulfate in vivo
1Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216, USA.
Abstract:
An opioid analgesic, morphine, and an opioid peptide, beta-endorphin, have been shown to induce chromosome damage, as indicated by an increased frequency of micronucleated lymphocytes, following acute administration to mice. The genotoxic response is opioid receptor-mediated and is abolished in adrenalectomized animals. Further, plasma from morphine-treated animals also induces micronuclei formation in naive lymphocytes in vitro; this response is blocked by inclusion the steroid antagonist RU 486 in the incubation mixture. In addition to the steroid-mediated production of chromosome damage, morphine acts directly on lymphocytes to enhance the clastogenicity of acutely administered cyclophosphamide in manner consistent with depressed DNA repair capacity.
Insights
Morphine and beta-endorphin cause chromosome damage in mice via opioid receptors, potentially mediated by steroids. This damage may involve direct effects on lymphocyte DNA repair.
Area of Science:
- Pharmacology
- Genetics
- Toxicology
Background:
- Opioid analgesics like morphine and endogenous opioid peptides such as beta-endorphin interact with opioid receptors.
- Chromosome damage, indicated by micronucleated lymphocytes, is a marker of genotoxicity.
- Steroid hormones play a role in various physiological processes, including stress responses.
Purpose of the Study:
- To investigate the genotoxic effects of morphine and beta-endorphin.
- To determine the role of opioid receptors and steroid mediation in this genotoxicity.
- To explore the direct effects of morphine on lymphocyte DNA repair capacity.
Main Methods:
- Acute administration of morphine and beta-endorphin to mice.
- Assessment of micronucleated lymphocyte frequency.
- Adrenalectomy in mice to assess steroid mediation.
- In vitro incubation of naive lymphocytes with plasma from morphine-treated animals.
- Use of the steroid antagonist RU 486.
- Assessment of morphine's effect on cyclophosphamide-induced clastogenicity in lymphocytes.
Main Results:
- Morphine and beta-endorphin administration increased micronucleated lymphocyte frequency in mice.
- The genotoxic response was opioid receptor-mediated and abolished in adrenalectomized animals.
- Plasma from morphine-treated mice induced micronuclei formation in naive lymphocytes in vitro.
- RU 486 blocked the in vitro micronuclei formation induced by plasma from morphine-treated mice.
- Morphine directly enhanced cyclophosphamide-induced clastogenicity in lymphocytes, suggesting impaired DNA repair.
Conclusions:
- Opioid administration induces chromosome damage through an opioid receptor-mediated pathway, involving steroid mediation.
- Morphine may also directly impair DNA repair mechanisms in lymphocytes.
- These findings highlight potential genotoxic risks associated with opioid use.