The Clastogenicity of Morphine Sulfate in vivo
An opioid analgesic, morphine, and an opioid peptide, β-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.
KeywordsChromosome Damage Morphine Sulfate Cytogenetic Damage Murine Lymphocyte Adrenalectomized Animal
Unable to display preview. Download preview PDF.
- Belknap JK, O’Toole LA (1991): Studies of genetic differences in response to opioid drugs. In JC Crabbe Jr,RA Harris (eds.), The Genetic Basis of Alcohol and Drug Actions, Plenum Press, NY, pp 225–252.Google Scholar
- Das RK, Swain N (1982): Mutagenic evaluation of morphine sulfate and pethidine hydrochloride in the mice by the micronucleus test. India J Med Res 75: 112–117.Google Scholar
- Dawson-Saunders B, Trapp RG (1994): Estimating and comparing means. In J Dolan, C Langan, K Hornyak(eds.), Basic and Clinical Biostatistics, 2nd ed., Paramount Publishing, Norwalk, pp 100–122.Google Scholar
- Falek A, Madden JJ, Donahoe RM, Shafer DA (1987): Genetic and immunologic consequences of opiate actions on lymphocytes. In MC Braude, AM Zimmerman (eds.), Genetic and Perinatal Effects of Abused Substances, Academic Press, San Diego, pp 43–67.Google Scholar
- Heddle JA, Krepinsky AB, Marshall RM (1983): Cellular sensitivity to mutagens and carcinogens in the chromosome-breakage and other cancer prone syndromes. In J German (ed.), Chromosome Mutation and Neoplasia, Liss, NY, pp 203–234.Google Scholar
- Sawant SG, Couch DB (1994a): The induction of micronuclei in murine lymphocytes by morphine. Environ Molec Mutagen, in press.Google Scholar
- Sawant SG, Couch DB (1994b): The role of adrenal corticosteroids in mediating morphine-induced clastogenicity to murine lymphocytes. Environ Molec Mutagen, submitted.Google Scholar
- Shafer DA, Falek A, Donahoe RM, Madden JJ (1990–91): Biogenetic effects of opiates. Internatl J Addictions 25: 1–18.Google Scholar