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Evoked potentials in rats with misonidazole neurotoxicity

I. Brain stem auditory evoked potentials

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Summary

Central neurotoxicity produced in rats by daily administration of 300 mg/ kg of misonidazole (MISO) 5 times/ week for 4–5 weeks (total dose = 6.0 gm/ kg) was evaluated weekly with brain stem auditory evoked potentials (BAEPs). Compared to untreated control rats, all treated rats had a prolongation of the I–IV interpeak latency (p < 0.005) at a mean of 13.2 ± 2.7 days at a cumulative dose of approximately 4.0 gm/ kg of MISO per rat. In some rats, the I–III and I–II interwave latencies were prolonged and waves III and IV were lost. Control rats did not show any significant alteration in BAEP latency or amplitude. Histopathologic examination of the brain stems of treated rats showed that necrotic lesions were present primarily in the nuclei of the tegmentum of the fourth ventricle, with scattered nuclear involvement in the cerebellar roof nuclei, inferior olive, and nucleus of the spinal tract of the trigeminal nerve. The cerebral cortex appeared to be normal in all treated rats. Changes in BAEPs caused by central neurotoxicity correlated with the histopathologic findings. We conclude that BAEPs are a sensitive method for evaluating MISO central neurotoxicity in the rat model.

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References

  1. Abratt RP, Blackburn JD: Loss of hearing after misonidazole. Br J Radiol 53:1208, 1980.

    Google Scholar 

  2. Adams GE, Fowler JF, Dische S, et al: Hypoxic cell sensitizers in radiotherapy. Lancet 1:186–188, 1976.

    Google Scholar 

  3. Asquith JC, Foster JL, Willson RL, et al: Metronidazole (‘Flagyl’). A radiosensitizer of hypoxic cells. Br J Radiol 47:474–481, 1974.

    Google Scholar 

  4. Begg AC, Sheldon PW, Foster JL: Demonstration of radiosensitization of hypoxic cells in solid tumours by metronidazole. Br J Radiol 47:399–404, 1974.

    Google Scholar 

  5. Bobbin RP, May JG, Lemoine RL: Effects of pentobarbital and ketamine on brain stem auditory potentials. Arch Otolaryngol 105:467–470, 1979.

    Google Scholar 

  6. Chapman JD, Reuvers AP, Borsa J: Effectiveness of nitrofuran derivatives in sensitizing hypoxic mammalian cells to x-rays. Br J Radiol 46:623–630, 1973.

    Google Scholar 

  7. Conroy P, Von Burg R, Penney DP, et al: Effects of acute and chronic misonidazole administration on peripheralnerve electrophysiology in mice. Br J Cancer 41:523–528, 1980.

    Google Scholar 

  8. Cooper J: Neurotoxicity of hypoxic cell radiosensitizers. Proceedings of a conference on radiozensitizers sponsored by the Division of Cancer Treatment, National Cancer Institute, National Institutes of Health. Bethesda, MD, 26 March, 1980.

    Google Scholar 

  9. Dische S, Gray AJ, Zanelli GD, et al: Clinical testing of the radiosensitizer Ro-07–0582. II. Radiosensitization of normal and hypoxic skin. Clin Radiol 27:151–157, 1976.

    Google Scholar 

  10. Dische S, Saunders MI, Lee ME, et al: Clinical testing of the radiosensitizer Ro-07–0582: experience with multiple doses. Br J Cancer 35:567, 1977.

    Google Scholar 

  11. Edwards ME, Bolger CA, Levin VA, et al: Evaluation of misonidazole peripheral neurotoxicity in rats by analysis of nerve trains evoked response. Int J Radiol Oncol Biol Phys 8:69–74, 1982.

    Google Scholar 

  12. Frick S, Hacker M: Radiosensitizersmisonidazole(MIS)and desmethylmisonidazole (DEMIS): A comparative intravenous (I.V.) toxicity study using beagle dogs. Proc Am Assoc Cancer Res, 22:263, 1981 (abstract).

    Google Scholar 

  13. Gilroy J, Lynn GE, Ristow GE, et al: Auditory evoked brain stem potentials in a case of ‘locked-in’ syndrome. Arch Neurol (Chic) 34:492–495, 1977.

    Google Scholar 

  14. Griffin JW, Price DL, Kuethe DO, et al: Neurotoxicity of misonidazole in rats. I. Neuropathology. Neurotoxicity 1:299–312, 1979.

    Google Scholar 

  15. Hirst DG, Vognovic B, Hobson B: Changes in nerve conduction velocity in the mouse after acute and chronic administration of nitroinidazoles. Br J Cancer 39:159–167, 1979.

    Google Scholar 

  16. Huang C: A comparative study of the brain auditory response in mammals. Brain Res 184:215–219, 1980.

    Google Scholar 

  17. Jewett DL: Volume-conducted potentials in response to auditory stimuli as detected by averaging in the cat. Electroenceph Clin Neurophysiol 28:609–618, 1970.

    Google Scholar 

  18. Jewett DL, Romano MN: Neonatal development of auditory system potentials averaged from the scalp of rat and cat. Brain Res 36:101–135, 1972.

    Google Scholar 

  19. Jewett DL, Williston JS: Auditory-evoked far fields averaged from the scalp of humans. Brain 94:681–696, 1971.

    Google Scholar 

  20. Johnson R, Gomer C, Ambrus J, et al: An investigation of the pharmacological and radiosensitizing effects of the 2-nitroimidazole Ro-07–0582 in primates. Br J Radiol 49:294, 1976.

    Google Scholar 

  21. Mamoli B, Wesseley P, Kogelnik HD, et al: Electroneurographic investigations of misonidazole polyneuropathy. Eur Neurol 18:405–414, 1979.

    Google Scholar 

  22. Nodar RH, Hahn J, Levine HL: Brain stem auditory evoked potentials in determining the site of lesions of brain stem gliomas in children. Laryngoscope 90:258–265, 1980.

    Google Scholar 

  23. Overgaard J: Effect of local hyperthermia on the acute toxicity of misonidazole in mice. Br J Cancer 39:96–98, 1979.

    Google Scholar 

  24. Rebert CS: Thebrain stem auditory evoked response as a tool in neuro-behavioral toxicology and medicine. Motivation, motor and sensory processes of the brain. Prog Brain Res 54:458–462, 1980.

    Google Scholar 

  25. Robertson DM, Wasan SM, Skinner DB: Ultrastructural features of early brain stem lesions of thiamine-deficient rats. Am J Pathol 52:1081–1097, 1968.

    Google Scholar 

  26. Rose GP, Dewar AJ, Stratford IJ: A biochemical method for assessing the neurotoxic effects of misonidazole in the rat. Br J Cancer 42:890–899, 1980.

    Google Scholar 

  27. Starr A, Hamilton AE: Correlation between confirmed sites of neurological lesions and abnormalities of far-field auditory brain stem responses. Electroenceph Clin Neurophysiol 41:595–608, 1976.

    Google Scholar 

  28. Stockard JJ, Stockard JE, Sharbrough FW: Brain stem auditory evoked potentials in neurology: Methodology, interpretation, clinical application. In: Aminoff M (ed) Electrodiagnosis in clinical neurology. Churchill-Livingstone, Edinburgh 1981, pp 370–413.

    Google Scholar 

  29. Stockard JJ, Stockard JE, Sharbrough FW: Detection and localization of occult lesions with brainstem auditory responses. Mayo Clin Proc 52:761–769, 1977.

    Google Scholar 

  30. Urtasun RC, Chapman JD, Feldstein ML, et al: Peripheral neuropathy related to misonidazole: Incidence and pathology. Br J Cancer (Suppl 111) 37:271, 1978.

    Google Scholar 

  31. Von Burg R, Conroy PJ, Passalacqua W: Peripheral electrophysiological parameters in mice treated with misonidazole. Br J Cancer 40:134–143, 1979.

    Google Scholar 

  32. Waltzman SB, Cooper JS: Nature and incidence of misonida-zole-produced ototoxicity. Arch Otolarngol 107:52–54, 1981.

    Google Scholar 

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Authors and Affiliations

  1. Section of Neurosurgery and the Department of Neurology, Ft. Miley Veterans Administration Hospital, San Francisco, California

    Michael S. B. Edwards Dr., Stephen K. Powers, Richard A. Baringer, Don L. Jewett, Catherine Bolger & Theodore L. Phillips

  2. Departments of Neurological Surgery, Orthopaedic Surgery, and Radiation Oncology, School of Medicine, University of California, 94143, San Francisco, CA, USA

    Michael S. B. Edwards Dr., Stephen K. Powers, Richard A. Baringer, Don L. Jewett, Catherine Bolger & Theodore L. Phillips

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  1. Michael S. B. Edwards Dr.
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  2. Stephen K. Powers
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  3. Richard A. Baringer
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  4. Don L. Jewett
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  5. Catherine Bolger
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  6. Theodore L. Phillips
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Edwards, M.S.B., Powers, S.K., Baringer, R.A. et al. Evoked potentials in rats with misonidazole neurotoxicity. J Neuro-Oncol 1, 115–123 (1983). https://doi.org/10.1007/BF00182956

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