The clastogenicity of morphine sulfate in vivo.
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.
Couch
D B
DB
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216, USA.
Sawant
S G
SG
D000315:Adrenalectomy; D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects; D005260:Female; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015162:Micronucleus Tests; D015735:Mifepristone / Q000494:pharmacology; D009020:Morphine / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D001615:beta-Endorphin / Q000633:toxicity
D009153:Mutagens; D015735:Mifepristone; D001615:beta-Endorphin; D009020:Morphine; D003520:Cyclophosphamide