The Clastogenicity of Morphine Sulfate in vivo

  • David B. Couch
  • Satin G. Sawant
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 373)


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.


Chromosome Damage Morphine Sulfate Cytogenetic Damage Murine Lymphocyte Adrenalectomized Animal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amarose AP, Schuster CR (1971): Chromosome analyses of bone marrow and peripheral blood in subjects with a history of illicit drug use. Arch Gen Psychiat 25: 181–186.PubMedCrossRefGoogle Scholar
  2. Bali DB, Singh JR, Singh H, Sandhu D (1990): In vitro and in vivo genotoxicity evaluation of hormonal drugs. I. Hydrocortisone. Environ Molec Mutagen 16: 250–254.CrossRefGoogle Scholar
  3. 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
  4. Claman HN, Moorhead JW, Benner WH (1971): Corticostcroids and lymphoid cells in vitro. I. Hydrocortisone lysis of human, guinea pig, and mouse thymus cells. J Lab Clin Med 78: 499–507.PubMedGoogle Scholar
  5. 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
  6. 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
  7. Erexson GL, Kligerman AD (1987): A modified mouse peripheral blood lymphocyte culture system for cytogenetic analysis. Environ Molec Mutagen 10: 377–386.CrossRefGoogle Scholar
  8. Falek A, Jordan RB, King BJ, Arnold PJ, Skelton WD (1972): Human chromosomes and opiates. Arch Gen Psychiatry 27: 511–515.PubMedCrossRefGoogle Scholar
  9. 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
  10. Fischman HK, Roizin L, Moralishvili E, Albu P, Ross D, Rainer JD (1983): Clastogenic effects of morphine in pregnant monkeys and their offspring. Mutat Res 118: 77–89.PubMedCrossRefGoogle Scholar
  11. Gibson A, Ginsburg M, Hall M, Hart SL (1979): The effects of opiate receptor agonists and antagonists on the stress-induced secretion of corticosterone in mice. Br J Pharmacol 65: 139–146.PubMedCrossRefGoogle Scholar
  12. Harris PD, Garret R (1972): Susceptibility of addicts to infection and neoplasia. N Engl J Med 287: 310.PubMedGoogle Scholar
  13. 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
  14. Heddle JA, Cimino MC, Hayashi M, Romagna F, Shelby MD, Tucker JD, Vanparys P, MacGregor JT (1991): Micronuclei as an index of cytogenetic damage: past, present, and future. Environ Molec Mutagen 18: 277–291.CrossRefGoogle Scholar
  15. Madden JJ, Falek A, Shafer DA, Glick JH (1979): Effects of opiates and demographic factors on DNA repair synthesis in human leukocytes. Proc Natl Acad Sci USA 76: 5769–5773.PubMedCrossRefGoogle Scholar
  16. Pechnick RN (1993): Effects of opioids on the hypothalamo-pituitary-adrenal axis. Annu Rev Pharmacol Toxicol 32: 353–382.CrossRefGoogle Scholar
  17. Sapira JD, Ball JC, Penn H (1970): Causes of death among institutionalized narcotic addicts. J Chronic Dis 22: 733–742.PubMedCrossRefGoogle Scholar
  18. Sawant SG, Couch DB (1994a): The induction of micronuclei in murine lymphocytes by morphine. Environ Molec Mutagen, in press.Google Scholar
  19. Sawant SG, Couch DB (1994b): The role of adrenal corticosteroids in mediating morphine-induced clastogenicity to murine lymphocytes. Environ Molec Mutagen, submitted.Google Scholar
  20. Shafer DA, Falek A, Madden JJ, Tadayon F, Pline M, Bokos PJ, Kuehnle JC, Mendelson J (1983): Parallel increases in sister-chromatid exchanges at base level and with UV treatment in human opiate users. Mutat Res 109: 73–82.PubMedCrossRefGoogle Scholar
  21. Shafer DA, Dunbar VG, Falek A, Donahoe RM, Madden JJ, Bokos PJ (1990): Enhanced assays detect increased chromosome damage and sister-chromatid exchanges in heroin addicts. Mutat Res 234: 327–336.PubMedCrossRefGoogle Scholar
  22. Shafer DA, Falek A, Donahoe RM, Madden JJ (1990–91): Biogenetic effects of opiates. Internatl J Addictions 25: 1–18.Google Scholar
  23. Shafer DA, Xie Y, Falek A (1994): Detection of opiate-enhanced increases in DNA damage, HPRT mutants,and the mutation frequency in human HUT-78 cells. Environ Molec Mutagen 23: 37–44.CrossRefGoogle Scholar
  24. Swain N, Das RK, Paul M (1980): Cytogenetic assay of potential mutagenicity in vivo of two narcotic analgesics. Mutat Res 78: 97–100.PubMedCrossRefGoogle Scholar
  25. Yahya MD, Watson RR (1987): Immunomodulation by morphine and marijuana. Life Sci 41: 2503–2510.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • David B. Couch
    • 1
  • Satin G. Sawant
    • 1
  1. 1.Department of Pharmacology and ToxicologyUniversity of Mississippi Medical CenterJacksonUSA

Personalised recommendations