Hostname: page-component-5c6d5d7d68-wp2c8 Total loading time: 0 Render date: 2024-08-23T10:46:02.827Z Has data issue: false hasContentIssue false

Early morphological and chemical changes induced by cisplatin in the guinea pig organ of Corti

Published online by Cambridge University Press:  29 June 2007

Spiro D. Comis
Affiliation:
Department of Physiology, University of Birmingham
Peter H. Rhys-Evans*
Affiliation:
Department of Otolaryngology, Queen Elizabeth Hospital, Birmingham.
Michel P. Osborne
Affiliation:
Department of Physiology, University of Birmingham
James O. Pickles
Affiliation:
Department of Physiology, University of Birmingham
David J. R. Jeffries
Affiliation:
Department of Otolaryngology, Manor Hospital, Walsall
Henry A. C. Pearse
Affiliation:
Department of Physiology, University of Birmingham
*
Mr. P. H. Rhys-Evans, ENT/Head and Neck Unit, The Royal Marsden Hospital, Fulham Road, London SW3.

Abstract

Guinea pigs were treated with a single dose of Cisplatin (5 mg IP). After 2–4 days the cochleas were prepared for morphological analysis by scanning electron microscopy and chemical analysis by X-ray dispersive microanalysis. Following Cisplatin, the bundles of stereocilia on the hair cells were found to be rough, disarrayed, fused, and finally absorbed. Significant increases were found in the levels of calcium, sulphur, and phosporus in the abnormal hair cells. It is suggested that the high calcium levels might be due to the inhibition of enzymes which normally keep cytoplasmic calcium low, and that some of the changes in the stereocilia might be secondary to this.

Type
Research Article
Copyright
Copyright © JLO (1984) Limited 1986

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aggarwal, S. K. and Niroomand-Rad, I. (1983) Effect of Cisplatin on the plasma membrane phosphatase activities in Ascites Sarcoma-180 cells: a cytochemical study. Journal of Histochemistry and Cytochemistry, 31: 307317.CrossRefGoogle Scholar
Binet, A. and Volfin, P. (1977) Effect of an anti-tumor platinum complex, Pt(II) diamino-toluene on mitochondrial membrane properties. Biochemica Biophysica Acta, 461: 182187.CrossRefGoogle Scholar
Burgess, D. R. and Prum, B. E. (1982) Reevaluation of brush border motility: calcium induces core filament solation and microvillar vesiculation. Journal of Cell Biology, 94: 97107.Google Scholar
Comis, S. D., Pickles, J. O. and Osborne, M. P. (1985) Osmium tetroxide postfixation in relation to the cross-linkage and spatial organization of stereocilia in the guinea-pig cochlea. Journal of Neurocytology, 14: 113130.Google Scholar
Corey, D. P. and Hudspeth, A. J. (1979) Ionic basis of the receptor potential in a vertebrate hair cell. Nature, 281: 675677.CrossRefGoogle Scholar
Fleischman, R. W., Stadnicki, S. W., Ethier, M. F. and Schaeppi, U. (1975) Ototoxicity of cis-dichlorodiam- mine platinum (II) in the guinea pig. Toxicology and Applied Pharmacology, 33: 320322.CrossRefGoogle Scholar
Flock, A. and Cheung, H. C. (1977) Actin filaments in sensory hairs of inner ear receptor cells. Journal of Cell Biology, 75: 339343.Google Scholar
Flock, A., Bretscher, A. and Weber, K. (1982) Immunohistochemical localization of several cytoskeletal proteins in inner ear sensory and supporting cells. Hearing Research, 7: 7589.Google Scholar
Glenney, J. R., Matsudaira, P. and Weber, K. (1982) Calcium control of the intestinal microvillus cytoskeleton. In Cheung, W. Y. (ed). Calcium and Cell Function, Vol III New York: Academic Press, pp. 357380.Google Scholar
Harder, H. C. and Rosenberg, B. (1970) Inhibitory effects of anti-tumor platinum compounds on DNA, RNA and protein synthesis in mammalian cells in vitro. International Journal of Cancer, 6: 207216.Google Scholar
Levi, J., Jacobs, C, Kalman, S. M., McTigue, M. and Weiner, M. W. (1980) Mechanism of cis-platinum nephrotoxicity: I. Effects of sulfhydryl groups in rat kidneys. Journal of Pharmacology and Experimental Therapeutics, 213: 545550.Google Scholar
Leyland-Jones, B., Morrow, C, Tate, S., Urmacher, C, Gordon, C. and Young, C. W. (1983) Cis-diamminedichloroplatinum (II) nephrotoxicity and its relationship to renal γ-glutamyl transpeptidase and glutathione. Cancer Research, 43: 60726076.Google Scholar
Osborne, M. P., Comis, S. D. and Pickles, J. O. (1984) Morphology and cross-linkage of stereocilia in the guinea pig labyrinth examined without the use of osmium as a fixative. Cell and Tissue Research, 237: 4348.CrossRefGoogle ScholarPubMed
Pickles, J. O., Comis, S. D. and Osborne, M. P. (1984) Cross-links between stereocilia in the guinea pig organ of Corti, and their possible relation to sensory transduction. Hearing Research, 15: 103112.Google Scholar
Pill, I. J., Meyer, D., Perlia, C. P. and Wolfe, V. I. (1974) Effects of cis-diamminedichloroplatinum (NSC-119875) on hearing function in man. Cancer Chemotherapy Reports Part I, 58: 871875.Google Scholar
Rhys-Evans, P., Comis, S. D., Osborne, M. P., Pickles, J. O. and Jeffries, D. J. R. (1985) Cross-links between stereocilia in the human organ of Corti. Journal of Laryngology and Otology, 99: 1119.Google Scholar
Ronquist, G. (1975) Structurally bound adenosine-triphosphate phosphohydrolase of the animal cell. In Christensen, H. N. (ed). Biological Transport Reading, Mass.W. A. Benjamin, pp. 272297.Google Scholar
Sand, O. (1975) Effects of different ionic environments on the mechano-sensitivity of lateral line organs in the mudpuppy. Journal of Comparative Physiology Series A, 102: 2742.Google Scholar
Schaefer, S. D., Wright, C. G., Post, J. D. and Frenkel, E. P. (1981) Cis-platinum vestibular toxicity. Cancer, 47: 857859.Google Scholar
Stadnicki, S. W., Fleischman, R. W., Schaeppi, U. and Merriam, P. (1975) Cis-dichlorodiammineplatinum (II) (NSC-119875): hearing loss and other toxic effects in rhesus monkeys. Cancer Chemotherapy Reports, 59: 467480.Google Scholar
Thalmann, R., Thalmann, I., Ise, I. and Paloheimo, S. (1977) Noxious effects upon cochlear metabolism. Laryngoscope, 87: 699721.Google Scholar
Zenner, H. P. (1981) Cytoskeletal and muscle-like elements in cochlear hair cells. Archives of Otorhinolaryngology, 230: 8192.Google Scholar