Mitochondrial toxicity of antiviral drugs

Luft, R. The development of mitochondrial medicine. Proc.natn. Acad. Sci. 91, 8731–8738 (1994).

Wallace, D.C. Mitochondrial genetics: a paradigm for aging and degenerative diseases? Science 256, 628–632 (1994).

Elion, G.B. Discovery, mechanism of action, and selectivity. J. med. Virol, (supp 1) 1, 2–6 (1993).

McGowan, J.J. et al. Overview of the preclinical development of an antiretroviral drug, 2′,3′-dideoxyinosine. Rev. infect. Dis. 12, S513–S521 (1990).

Prusoff, W., Lin, T.-S., Pivazyan, A., Sun, A.S. & Birks, E. Empirical and rational approaches for development of inhibitors of the human immunodeficiency virus-HIV-1. Pharmac. Ther. 60, 315–329 (1993).

Mitsuya, H., Yarchoan, R. & Broder, S. Molecular targets for AIDS therapy. Science 249, 1533–1544 (1990).

Dalakas, M.C., Illa, I., Pezeshkpour, G., Laukaitis, J., Cohen, B. & Griffin, J. Mitochondrial myopathy caused by long term zidovudine therapy. New Engl. J. Med. 322, 1098–1105 (1990).

Lewis, W., Simpson, J.F. & Meyer, R.R. Cardiac mitochondrial DNA polymerase-γ is inhibited competitively and noncompetitively by phosphorylated zidovudine. Circulation Res 74, 344–348 (1994).

Cui, L., Toon, S., Schinazi, R.F. & Sommadossi, J.-P. Cellular and molecular events leading to mitochondrial toxicity of 1-[2′-deoxy-2′-fluoro-β-D-arabino-furanosyl]-5-iodouracil in human liver cells. J. clin. Invest. 95, 555–563 (1995).

Brahams, D. Deaths in US fialuridine trial. Lancet 343, 1494–1495 (1994).

Marshall, E. Drug trial deaths deemed unavoidable. Science 264, 1530 (1994).

Macilwain, C. US health agencies at odds over trial deaths. Nature 369, 433 (1994).

Rozencweig, M. et al. Overview of phase 1 trials of 2′,3′-dideoxyinosine (ddI) conducted on adult patients. Rev. infect. Dis. 12, S570S575 (1990).

Butler, K.M. et al. Dideoxyinosine in children with symptomatic human immunodeficiency virus infection. New Engl. J. Med. 324, 137–144 (1993).

Freiman, J.P., Helfert, K.E., Hamrell, M.R. & Stein, D.S. Hepatomegaly with severe steatosis in HIV-seropositive patients. AIDS 7, 379–385 (1993).

d'Amati, G., Kwan, W. & Lewis, W. Dilated cardiomyopathy in a zidovudine treated AIDS patient. Cardiovasc. Pathol. 1, 317–320 (1992).

Chang, C.-N., Skalski, V., Zhou, J.H. & Cheng, Y-C. Biochemical pharmacology of (+)- and (−)-2′,3′-dideoxy-3′-thiacytidine as anti-hepatitis B virus agents. J. biol. Chem. 267, 22414–22420 (1992).

Reichard, P. Interactions between deoxyribonucleotide and DNA. Annu. Rev. Biochem. 57, 349–374 (1988).

Munch-Petersen, B., Cloos, L., Tyrsted, G. & Eriksson, S. Diverging substrate specificity of pure human thymidine kinase 1 and 2 against antiviral dideoxynucleosides. J. biol. Chem. 266, 9032–9038 (1991).

Fry, M. & Loeb, L.A. Animal Cell DNA Pofymerases 221 (CRC Press, Boca Raton, Florida, 1986).

Wang, T.S.F. Eukaryotic DNA polymerases. Annu. Rev. Biochem. 60, 513–552 (1991).

Wallace, D.C. Diseases of the mitochondrial DNA. Annu. Rev. Biochem. 61, 1175–1212 (1992).

Wallace, D.C. Mitochondrial DNA sequence variation in human evolution and disease. Proc. natn. Acad. Sci. U. S. A. 91, 8739–8746 (1994).

Wright, G.E. & Brown, N.C. Deoxyribonucleotide analogs as inhibitors and substrates of DNA polymerases. Pharmac. Ther. 47, 447–497 (1990).

Dixon, M. & Webb, E.C. Enzymes 3rd edn. (Academic, New York, 1979).

Richmann, D.D. et al. The toxicity of AZT in the treatment of patients with AIDS and AIDS-related complex. New Engl. J. Med. 317, 192–197 (1987).

Yarchoan, R., Mitsuya, H., Myers, C.E. & Broder, S. Clinical pharmacology of 3′-azido-2′,3′-dideoxythymidine (zidovudine) and related dideoxynucleosides. New Engl. J. Med. 321, 726–738 (1989).

Nickel, W., Austermann, S., Bialek, G. & Grosse, F. Interactions of azidothymidine triphosphate with the cellular DNA polymerases α, β, and and with DNA Primase. J. biol. Chem. 267, 848–854 (1992).

Dainiak, N., Worthington, M., Riordan, M.A., Kreczko, S. & Goldman, L. 3′-Azido-3′-deoxythymidine (AZT) inhibits proliferation in vitro of human haematopoietic progenitor cells. Br. J. Haematol. 69, 299–304 (1988).

Scadden, D.T., Zon, L.I. & Groopman, J.E. Pathophysiology and management of HIV-associated hematologic disorders. Blood 74, 1455–1463 (1989).

Hamburger, A.W. & Chen, R.-B. Amelioration of azidothymidine-induced erythroid toxicity by hemin and stem cell factor in immune-suppressed mice. Exp. Hematol. 22, 348–352 (1994).

Yoshida, Y. & Yoshida, C. Reversal of azidothymidine-induced bone marrow suppression by 2′,3′-dideoxythymidine as studied by hemopoietic clonal culture. AIDS Res. hum. Retrovir. 6, 929–932 (1990).

Falcone, A., Darnowski, J.W., Ruprecht, R.M., Chu, S.H., Brunetti, I. & Calabresi, P. Different effect of benzylacyclouridine on the toxic and therapeutic effects of azidothymidine in mice. Blood 76, 2216–2221 (1990).

Rötig, A. et al. Pearson's marrow-pancreas syndrome. J. clin. Invest. 86, 1601–1608 (1990).

Arnaudo, E., Dalakas, M.C., Shanske, S., Moraes, C.T., DiMauro, S. & Schoen, E.A. Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy. Lancet 337, 508–510 (1991).

Pezeshkpour, G., Illa, I. & Dalakas, M.C. Ultrastructural characteristics and DNA immunocytochemistry in human immunodeficiency virus and zidovudine-associated myopathies. Hum. Pathol. 22, 1281–1288 (1991).

Lewis, W., Chomyn, A., Gonzalez, B. & Papoian, T. Zidovudine induces molecular, biochemical and Ultrastructural changes in rat skeletal muscle mitochondria. J. clin. Invest. 89, 1354–1360 (1992).

Lewis, W. et al. Mitochondrial Ultrastructural and molecular changes induced by zidovudine in rat hearts. Lab Invest. 65, 228–236 (1991).

Lamperth, L., Dalakas, M.C., Dagani, F., Anderson, J. & Ferrari, R. Abnormal skeletal and cardiac mitochondria induced by zidovudine (AZT) in human muscle in vitro and in an animal model. Lab Invest. 65, 742–751 (1991).

Dalakas, M.C. Carnitine loss and AZT-myopathy. Ann. Neurol. 36, 680–681 (1994).

Chariot, P. & Gherardi, R. Partial cytochrome c oxidase deficiency and cyto-plasmic bodies in patients with zidovudine myopathy. Neuromusc. Dis. 5, 357–363 (1991).

Chariot, P. et al. Blood lactate/pyruvate ratio is a non invasive test for the diagnosis of zidovudine myopathy. Arthritis Rheumat. 37, 583–586 (1994).

Weissman, J.D., Constantinides, I., Hudgins, P. & Wallace, D.C. 31P magnetic resonance spectroscopy suggests impaired mitochondrial functions in AZT-treated HIV-infected patients. Neurology 42, 619–623 (1992).

Dalakas, M.C., Monzon, M.E., Bernardini, I., Gahl, W.A. & Jay, C.A. Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage. Ann. Neurol. 35, 483–487 (1994).

Mhiri, C. et al. Zidovudine myopathy: a distinctive disorder associated with mitochondrial dysfunction. Ann. Neurol 29, 606–614 (1991).

Peters, R.S., Winer, J., Landon, D.N., Stotter, A. & Pinching, A.J. Mitochondrial myopathy associated with chronic zidovudine therapy in AIDS. Q. J. Med. 86, 5–15 (1993).

Jay, C., St Dalakas, M.C. Myopathies and neuropathies in HIV-infected adults and children. in Pediatric Aids (Williams & Wilkins, Baltimore, 1994)

Semino-Mora, M.C., Leon-Monzon, M.E. & Dalakas, M.C. The effect of L-carnitine on the AZT-induced destruction of human myotubes. Part 1: L-Carnitine prevents the myotoxicity of AZT in vitro. Lab. Invest. 70, 102–112 (1994).

d'Amati, G. & Lewis, W. Zidovudine azidothymidine causes early increases in mitochondrial ribonucleic acid abundance and induces Ultrastructural changes in cultured mouse muscle cells. Lab. Invest. 71, 879–884 (1994).

Herskowitz, A., Willoughby, S.B., Baughman, K.L., Schulman, S.P. & Bartlett, J.D. Cardiomyopathy associated with antiretroviral therapy in patients with HIV infection: a report of 6 cases. Ann. intern. Med. 116, 311–313 (1992).

Lipschultz, S.E., Gray, J., Sanders, S.P., Hale, A.R., Mclntosh, K. & Colan, S.D. Cardiac structure and function in children with human immunodeficiency virus infection treated with zidovudine. New Engl. J. Med. 327, 1260–1265 (1992).

Chatta, G., Arieff, A.I., Cummings, C. & Tierney, L.M. Lactic acidosis complicating the acquired immunodeficiency syndrome. Ann. intern. Med. 118, 37–39 (1993).

Jolliet, P. & Widman, J.J. Reye's syndrome in adult with AIDS. Lancet 335, 1457 (1990).

Dubinsky, R.M., Yarchoan, R., Dalakas, M.C. & Broder, S. Reversible axonal neuropathy from the treatment of AIDS and related disorders with 2′,3′-dideoxycytidine (ddC). Muscle Nerve 12, 856–860 (1989).

Anderson, T.D. et al. Mitochondrial schwannopathy and peripheral myelinopathy in a rabbit model of dideoxycytidine neurotoxicity. Lab Invest. 70, 724–739 (1994).

Jay, C., Ropka, M. & Dalakas, M.C. The drugs 2′,3′-dideoxyinosine (ddl) and 2′,3′-dideoxycytidine (ddC) are safe alternatives in people with AIDS with, zidovudine-induced myopathy. J. AIDS 7, 630–631 (1994).

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′-deoxythymidine. J. biol. Chem. 264, 11934–11937 (1989).

Keilbaugh, S.A., Prusoff, W.H. & Simpson, M.V. The PC 12 cell as a model for studies of mechanism of induction of peripheral neuropathy by anti-HIV-1 dideoxynucleoside analogs. Biochem. Pharmacol. 42, R5–R8 (1991).

Fourel, I., Li, J., Hantz, O., Jacquet, C., Fox, J.J. & Trepo, C. Effects of 2′-fluorinated arabinosyl-pyrimidine nucleosides on duck hepatitis B virus DNA level in serum and liver of chronically infected ducks. J. med. Virol. 37, 122–126 (1992).

Lewis, W., Simpson, J.F., Meyer, R.R., Colacino, J.M. & Perrino, F.W. Mammalian DNA polymerases α, β, γ, δ, and incorporate fialuridine (FIAU) monophosphate into DNA and are inhibited competitively by FIAU triphos-phate. Biochemistry 33, 14620–14624 (1994).

Richardson, F.C., Engelhardt, J.A. & Bowsher, R.R. Fialuridine accumulates in DNA of dogs, monkeys, and rats following long-term oral administration. Proc. natn. Acad. Sci. U. S. A. 91, 12003–12007 (1994).

Moraes, C.T. et al. mtDNA depletion with variable tissue expression: an novel genetic abnormality in mitochondrial diseases. Am. J. hum. Genet. 48, 492–501 (1991).

Progress in Neuropathy Vol 7 (eds. Sato, T. & DiMauro, S.) (Raven Press, New York, 1991).

Morgan-Hughes, J.A. Mitochondrial diseases. in Myology (eds. Engel, A. G. & Franzini-Armstrong, C.) 1610–1660 (McGraw Hill, New York, 1994).

Shoffner, J.M.V.I. & Wallace, D.C. Oxidative phosphorylation diseases. Disorder of two genomes. Adv. hum. Genet. 19, 267–330 (1990).

Moraes, C.T. et al. Mitochondrial DNA in human pathology, (eds. DiMauro, S. & Wallace, D. C.) 97–108 (Raven, New York, 1993).