Induction of micronuclei in murine lymphocytes by morphine
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Published on: July 29, 2014
1Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216, USA.
Abstract:
Although individuals who abuse drugs are prone to an increased risk of malignancy, the mutagenic and carcinogenic potential of these agents has received relatively little attention. We report here on the potential of morphine to induce micronuclei in murine lymphocytes. Following a single intraperitoneal injection of 20 mg/kg morphine, the frequency of micronucleated binuclear (cytochalasin-blocked) murine T- and B-splenocytes was elevated from 12-36 hr after treatment. The maximum frequencies seen 24 hr after injection were 6.3- and 4.9-fold greater than the respective controls. A dose-dependent induction of micronuclei was observed from 5-20 mg/kg morphine, with no further increases in frequency produced by higher doses. In contrast, incubation of mitogen-stimulated splenocytes with 10(-7)-10(-4) M morphine in vitro produced no change in frequency of micronucleated cells relative to controls. Treatment with the narcotic antagonist naloxone (5 mg/kg) alone had no effect on the frequency of micronuclei, but reduced the clastogenic response of a subsequently administered dose of morphine (20 mg/kg). Thus, in murine lymphocytes morphine indirectly produces genetic damage, which is at least in part opioid receptor-mediated.
Insights
Morphine exposure increases the risk of genetic damage in mouse lymphocytes, indicated by elevated micronuclei. This effect is dose-dependent and mediated by opioid receptors, suggesting potential carcinogenic risks.
Area of Science:
- Toxicology
- Genetics
- Pharmacology
Background:
- Drug abuse is linked to increased cancer risk, yet the mutagenic potential of abused drugs is understudied.
- Morphine, a widely used opioid, has not been thoroughly investigated for its genotoxic effects.
Purpose of the Study:
- To investigate the potential of morphine to induce genetic damage, specifically micronuclei formation, in murine lymphocytes.
- To determine if morphine's genotoxic effects are dose-dependent and mediated by opioid receptors.
Main Methods:
- Murine splenocytes were analyzed for micronuclei formation after single intraperitoneal injections of morphine at various doses.
- Splenocytes were also incubated with morphine in vitro to assess direct effects.
- The role of opioid receptors was examined using the antagonist naloxone.
Main Results:
- Morphine administration significantly increased the frequency of micronucleated splenocytes in a dose-dependent manner.
- The genotoxic effect was observed from 12-36 hours post-injection, with peak effects at 24 hours.
- In vitro incubation with morphine did not induce micronuclei, suggesting an indirect mechanism.
- Naloxone blocked morphine's genotoxic effect, indicating opioid receptor involvement.
Conclusions:
- Morphine induces indirect genetic damage in murine lymphocytes, evidenced by micronuclei formation.
- The genotoxicity of morphine is at least partially mediated through opioid receptors.
- These findings highlight the potential mutagenic and carcinogenic risks associated with morphine exposure.
