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. 1992 Sep;36(9):2061–2065. doi: 10.1128/aac.36.9.2061

Ultrastructural changes associated with reduced mitochondrial DNA and impaired mitochondrial function in the presence of 2'3'-dideoxycytidine.

L D Lewis 1, F M Hamzeh 1, P S Lietman 1
PMCID: PMC192440  PMID: 1329643

Abstract

Incubation of Molt-4 cells in 4 microM 2'3'-dideoxycytidine did not produce a significant change in the mitochondrial ultrastructure after 4 days; however, by 12 days, the mitochondrial ultrastructure was distorted, with condensed cristae or vacuolization, or both. Concentration-dependent decreases in both cell growth (mean 50% inhibitory concentration, 4.70 +/- 0.5 microM) and mitochondrial DNA content (mean 50% inhibitory concentration, 0.46 +/- 0.06 microM) occurred after incubation with 2'3'-dideoxycytidine for 4 days.

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Selected References

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  1. Bomb B. S., Bedi H. K. Chloramphenicol--induced peripheral neuropathy (a case report). J Assoc Physicians India. 1974 Aug;22(8):623–625. [PubMed] [Google Scholar]
  2. Chen C. H., Cheng Y. C. Delayed cytotoxicity and selective loss of mitochondrial DNA in cells treated with the anti-human immunodeficiency virus compound 2',3'-dideoxycytidine. J Biol Chem. 1989 Jul 15;264(20):11934–11937. [PubMed] [Google Scholar]
  3. Cheng Y. C., Dutschman G. E., Bastow K. F., Sarngadharan M. G., Ting R. Y. Human immunodeficiency virus reverse transcriptase. General properties and its interactions with nucleoside triphosphate analogs. J Biol Chem. 1987 Feb 15;262(5):2187–2189. [PubMed] [Google Scholar]
  4. Cooney D. A., Dalal M., Mitsuya H., McMahon J. B., Nadkarni M., Balzarini J., Broder S., Johns D. G. Initial studies on the cellular pharmacology of 2',3-dideoxycytidine, an inhibitor of HTLV-III infectivity. Biochem Pharmacol. 1986 Jul 1;35(13):2065–2068. doi: 10.1016/0006-2952(86)90571-x. [DOI] [PubMed] [Google Scholar]
  5. Dalakas M. C., Illa I., Pezeshkpour G. H., Laukaitis J. P., Cohen B., Griffin J. L. Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med. 1990 Apr 19;322(16):1098–1105. doi: 10.1056/NEJM199004193221602. [DOI] [PubMed] [Google Scholar]
  6. Furman P. A., Fyfe J. A., St Clair M. H., Weinhold K., Rideout J. L., Freeman G. A., Lehrman S. N., Bolognesi D. P., Broder S., Mitsuya H. Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8333–8337. doi: 10.1073/pnas.83.21.8333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Godel V., Nemet P., Lazar M. Chloramphenicol optic neuropathy. Arch Ophthalmol. 1980 Aug;98(8):1417–1421. doi: 10.1001/archopht.1980.01020040269011. [DOI] [PubMed] [Google Scholar]
  8. Hamzeh F. M., Lietman P. S., Gibson W., Hayward G. S. Identification of the lytic origin of DNA replication in human cytomegalovirus by a novel approach utilizing ganciclovir-induced chain termination. J Virol. 1990 Dec;64(12):6184–6195. doi: 10.1128/jvi.64.12.6184-6195.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. King M. E., Godman G. C., King D. W. Respiratory enzymes and mitochondrial morphology of HeLa and L cells treated with chloramphenicol and ethidium bromide. J Cell Biol. 1972 Apr;53(1):127–142. doi: 10.1083/jcb.53.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Klecker R. W., Jr, Collins J. M., Yarchoan R. C., Thomas R., McAtee N., Broder S., Myers C. E. Pharmacokinetics of 2',3'-dideoxycytidine in patients with AIDS and related disorders. J Clin Pharmacol. 1988 Sep;28(9):837–842. doi: 10.1002/j.1552-4604.1988.tb03225.x. [DOI] [PubMed] [Google Scholar]
  11. Merigan T. C., Skowron G., Bozzette S. A., Richman D., Uttamchandani R., Fischl M., Schooley R., Hirsch M., Soo W., Pettinelli C. Circulating p24 antigen levels and responses to dideoxycytidine in human immunodeficiency virus (HIV) infections. A phase I and II study. Ann Intern Med. 1989 Feb 1;110(3):189–194. doi: 10.7326/0003-4819-110-3-189. [DOI] [PubMed] [Google Scholar]
  12. Merigan T. C., Skowron G. Safety and tolerance of dideoxycytidine as a single agent. Results of early-phase studies in patients with acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex. Study Group of the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. Am J Med. 1990 May 21;88(5B):11S–15S. doi: 10.1016/0002-9343(90)90415-a. [DOI] [PubMed] [Google Scholar]
  13. Mitsuya H., Broder S. Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1911–1915. doi: 10.1073/pnas.83.6.1911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Peyronnard J. M., Charron L., Bellavance A., Marchand L. Neuropathy and mitochondrial myopathy. Ann Neurol. 1980 Mar;7(3):262–268. doi: 10.1002/ana.410070310. [DOI] [PubMed] [Google Scholar]
  15. Pezeshkpour G., Krarup C., Buchthal F., DiMauro S., Bresolin N., McBurney J. Peripheral neuropathy in mitochondrial disease. J Neurol Sci. 1987 Feb;77(2-3):285–304. doi: 10.1016/0022-510x(87)90129-8. [DOI] [PubMed] [Google Scholar]
  16. Ramilo O., Kinane B. T., McCracken G. H., Jr Chloramphenicol neurotoxicity. Pediatr Infect Dis J. 1988 May;7(5):358–359. doi: 10.1097/00006454-198805000-00015. [DOI] [PubMed] [Google Scholar]
  17. Rotig A., Colonna M., Bonnefont J. P., Blanche S., Fischer A., Saudubray J. M., Munnich A. Mitochondrial DNA deletion in Pearson's marrow/pancreas syndrome. Lancet. 1989 Apr 22;1(8643):902–903. doi: 10.1016/s0140-6736(89)92897-3. [DOI] [PubMed] [Google Scholar]
  18. SCOTT J. L., FINEGOLD S. M., BELKIN G. A., LAWRENCE J. S. A CONTROLLED DOUBLE-BLIND STUDY OF THE HEMATOLOGIC TOXICITY OF CHLORAMPHENICOL. N Engl J Med. 1965 Jun 3;272:1137–1142. doi: 10.1056/NEJM196506032722201. [DOI] [PubMed] [Google Scholar]
  19. Shuster R. C., Rubenstein A. J., Wallace D. C. Mitochondrial DNA in anucleate human blood cells. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1360–1365. doi: 10.1016/s0006-291x(88)81291-9. [DOI] [PubMed] [Google Scholar]
  20. Simpson M. V., Chin C. D., Keilbaugh S. A., Lin T. S., Prusoff W. H. Studies on the inhibition of mitochondrial DNA replication by 3'-azido-3'-deoxythymidine and other dideoxynucleoside analogs which inhibit HIV-1 replication. Biochem Pharmacol. 1989 Apr 1;38(7):1033–1036. doi: 10.1016/0006-2952(89)90245-1. [DOI] [PubMed] [Google Scholar]
  21. Skinnider L. F., Ghadially F. N. Chloramphenicol-induced mitochondrial and ultrastructural changes in hemopoietic cells. Arch Pathol Lab Med. 1976 Nov;100(11):601–605. [PubMed] [Google Scholar]
  22. Starnes M. C., Cheng Y. C. Cellular metabolism of 2',3'-dideoxycytidine, a compound active against human immunodeficiency virus in vitro. J Biol Chem. 1987 Jan 25;262(3):988–991. [PubMed] [Google Scholar]
  23. Yarchoan R., Broder S. Development of antiretroviral therapy for the acquired immunodeficiency syndrome and related disorders. A progress report. N Engl J Med. 1987 Feb 26;316(9):557–564. doi: 10.1056/NEJM198702263160925. [DOI] [PubMed] [Google Scholar]
  24. Yunis A. A., Smith U. S., Restrepo A. Reversible bone marrow suppression from chloramphenicol. A consequence of mitochondrial injury. Arch Intern Med. 1970 Aug;126(2):272–275. [PubMed] [Google Scholar]
  25. Zimmermann W., Chen S. M., Bolden A., Weissbach A. Mitochondrial DNA replication does not involve DNA polymerase alpha. J Biol Chem. 1980 Dec 25;255(24):11847–11852. [PubMed] [Google Scholar]

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