|
Sign In to gain access to subscriptions and/or personal tools.
|
Olfactory Epithelial Lesions Induced by Various Cancer Chemotherapeutic Agents in Mice
Kiyonori Kai
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo 134-8630, Japan, kaikitrx{at}daiichipharm.co.jp
Hiroshi Satoh
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo 134-8630, Japan
Tetsuyo Kajimura
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo 134-8630, Japan
Michiyuki Kato
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo 134-8630, Japan
Kazuyuki Uchida
Department of Veterinary Pathology, Faculty of Agriculture, Miyazaki University, Miyazaki 889-2155, Japan
Ryoji Yamaguchi
Department of Veterinary Pathology, Faculty of Agriculture, Miyazaki University, Miyazaki 889-2155, Japan
Susumu Tateyama
Department of Veterinary Pathology, Faculty of Agriculture, Miyazaki University, Miyazaki 889-2155, Japan
Kazuhisa Furuhama
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo 134-8630, Japan
In order to examine and compare the potential toxicity in the olfactory epithelium, the antitumor drug vincristine sulfate (VCR), vinblastine sulfate (VBL), vindesine sulfate (VDS), paclitaxel (PTX), mitomycin C (MMC), 5-fluorouracil, (5-FU) or cisplatin (CDDP) was intravenously injected once (designated as day 1) at an estimated 10% lethal dose (LD10) to male BALB/c mice. The animals were necropsied on days 2, 5 and 15, and nasal tissues were examined by light-microscopy, counting of epithelial cells positive for terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL), immunohistochemical staining with keratin antibody, and electron microscopy. Further, to delineate the drug disposition in the target organ, whole-body radioluminography was performed 1 hour and 24 hours after treatment with the LD10 of PTX or 5-FU. Of the antitumor drugs employed, only the antimicrotubule agents, VCR, VBL, VDS, and PTX, induced single cell death in the olfactory epithelium, especially sensory cells on day 2, atrophy of the olfactory epithelium on day 5, and myelin fragmentation in the trigeminal nerve on day 15. PTX induced the strongest changes among the 4 antimicrotubule agents. The cell death was confirmed to be apoptosis by TUNEL assay and electron microscopy, whereas the change in horizontal basal cells of the olfactory epithelium was shown not to be apoptosis by keratin staining. In quantitative radioluminography, radioactivity of PTX in the nasal tissues both 1 hour and 24 hours after administration was about 4- or 5-fold higher than those of 5-FU. These results suggest that tubulin-targeting antitumour drugs could induce apoptosis in the olfactory epithelial cells of mice and that high drug distribution may effect the onset of the olfactory lesions.
Key Words: Antitumor drugs • olfactory toxicity • sensory cells • apoptosis • mice.
References
- Barber, P.C., and Raisman, G. (1978). Cell division in the vomeronasal organ of the adult mouse. Brain Res 141, 57—66.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Bayssas, M., Gouveia, J., de Vassal, F., Misset, J.L., Schwarzenberg, L., Ribaud, P., Musset, M., Jasmin, C., Hayat, M., and Mathe, G. (1980). Vindesine: a new vinca alkaloid. Recent Results Cancer Res 74, 91—7.[Medline]
[Order article via Infotrieve]
- Brenneman, K.A., Meleason, D.F., Sar, M., Marshall, M.W., James, R.A., Gross, E.A., Martin, J.T., and Dorman, D.C. (2002). Olfactory mucosal necrosis in male CD rats following acute inhalation exposure to hydrogen sulfide: reversibility and the possible role of regional metabolism. Toxicol Pathol 30, 200—8.[Abstract/Free Full Text]
- Cleton, F.J. (1995). Chemotherapy: general aspects. In Oxford Textbook of Oncology (Peckham, M., Pinedo, H., Veronesi, V., eds.), pp. 445—53. Oxford University Press, Oxford.
- Gottschalk, P.G., Dyck, P.J., and Kiely, J.M. (1968). Vinca alkaloid neuropathy: nerve biopsy studies in rats and in man. Neurology 9, 875—82.
- Hirano, G., and Miyazaki, K. (1998). Anosmia caused by fluorouracil derivatives. Nichi Kan Yakuji 40, 877—9.
- Huard, J.M., and Schwob, J.E. (1995). Cell cycle of globose basal cells in rat olfactory epithelium. Dev Dyn 203, 17—26.[Web of Science][Medline]
[Order article via Infotrieve]
- Japanese Association for Laboratory Animal Science (1987). Guidelines for animal experimentation. Exp Anim 36, 285—8.
- Kai, K., Satoh, H., Kashimoto, Y., Kajimura, T., and Furuhama, K. (2002). Olfactory epithelium as a novel toxic target following an intravenous administration of vincristine to mice. Toxicol Pathol 30, 306—11.[Abstract/Free Full Text]
- Kanter, P.M., Klaich, G.M., Bullard, G.A., King, J.M., Bally, M.B., and Mayer, L.D. (1994). Liposome encapsulated vincristine: preclinical toxicologic and pharmacologic comparison with free vincristine and empty liposome in mice, rats, and dogs. Anticancer Drug 5, 579—90.[CrossRef][Medline]
[Order article via Infotrieve]
- Kastner, A., Moyse, E., Bauer, S., Jourdan, F., and Brun, G. (2000). Unusual regulation of cyclin D1 and cyclin-dependent kinases cdk2 and cdk4 during in vivo mitotic stimulation of olfactory neuron progenitors in adult mouse. J Neurochem 74, 2343—9.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Kohler, D.R., and Goldspiel, B.R. (1994). Paclitaxel (taxol). Pharmacotherapy 14, 3—34.[Web of Science][Medline]
[Order article via Infotrieve]
- Koja, S., Itokazu, T., Kamiya, S., Maeshiro, N., Yamauchi, M., Esu, H., Simoji, Y., Kanazawa, T., and Noda, Y. (1994). Tissue concentration of tegafur suppository in patients with head and neck cancer concentration of 5-FU in cancer tissue. Gan To Kagaku Ryoho 21, 981—5.[Medline]
[Order article via Infotrieve]
- Kuhn, J.G. (2001). Fluorouracil and the new oral fluorinated pyrimidines. Ann Pharmacother 35, 217—27.[Abstract]
- Mery, S., Gross, E.A., Joyner, D.R., Godo, M., and Morgan, K.T. (1994). Nasal diagram: a tool for recording the distribution of nasal lesion in rats and mice. Toxicol Pathol 22, 353—72.[Abstract/Free Full Text]
- Morgan, K.T. (1994). Nasal dosimetry, lesion distribution, and the toxicologic pathologist: a brief review. Inhal Toxicol 6, 41—57.[Web of Science]
- Morgan, K.T., and Harkema, J.R. (1996). Nonneoplastic lesions of the olfactory mucosa, In Respiratory System, Monographs on Pathology of Laboratory Animals, 2nd ed. (T. C. Jones, D. L. Dungworth, and U. Mohr, eds.). pp. 28—43. Springer-Verlag Berlin Heidelberg, New York.
- Nakamura, H., Nonomura, N., Fujiwara, M., and Nakano, Y. (1995). Olfactory disturbances caused by the anti-cancer drug tegafur. Eur Arch Otorhinolaryngol 252, 48—52.[Medline]
[Order article via Infotrieve]
- O'Marcaigh, A.S., and Betcher, D.L. (1995). The vinca alkaloids. J Pediatr Oncol Nurs 12, 140—2.[Free Full Text]
- Onetto, N., Canetta, R., Winograd, B., Catane, R., Dougan, M., Grechko, J., Burroughs, J., and Rozencweig, M. (1993). Overview of taxol safety. J Natl Cancer Inst Monogr 15, 131—9.
- Quasthoff, S., and Hartung, H.P. (2002). Chemotherapy-induced peripheral neuropathy. J Neurol 249, 9—17.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Reed, E. (1999). Cisplatin. Cancer Chemother Biol Response Modif 18, 144—51.[Medline]
[Order article via Infotrieve]
- Robinson, D.A., Foster, J.R., Nash, J.A., and Reed, C.J. (2003). Three-dimensional mapping of the lesions induced by beta-beta'iminodiproprionitrile, methyl iodide and methyl methacrylate in the rat nasal cavity. Toxicol Pathol 31, 340—7.[Abstract/Free Full Text]
- Schwartz, L.M., Chikaraishi, D.M., and Kauer, J.S. (1991). Characterization of potential precursor populations in the mouse olfactory epithelium using immunocytochemistry and autoradiography. J Neurosci 11, 3556—64.[Abstract]
- Suzuki, Y., and Takeda, M. (1991). Basal cells in the mouse olfactory epithelium after axotomy: immunohistochemical and electoton-microscopic studies. Cell Tissue Res 266, 239—45.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Suzuki, Y., Takeda, M., and Farbman, A.I. (1996). Supporting cells as phagocyte in the olfactory epithelium after bulbectomy. J Comp Neurol 376, 509—17.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Suzuki, Y., Takeda, M., Obara, N., and Suzuki, N. (1998). Bulbectomy of neonatal mice induces migration of basal cells from the olfactory epithelium. Brain Res Dev Brain Res 108, 295—298.[CrossRef][Medline]
[Order article via Infotrieve]
- Suzuki, Y., Takeda, M., Obara, N., Suzuki, N., and Takeichi, N. (2000). Olfactory epithelium consisting of supporting cells and horizontal basal cells in the posterior nasal cavity of mice. Cell Tissue Res 299, 313—25.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Todd, G.C., Gibson, W.R., and Morton, D.M. (1976). Toxicology of vindesine (desacetyl vinblastine amide) in mice, rats, and dogs. J Toxicol Environ Health 1, 843—50.[Web of Science][Medline]
[Order article via Infotrieve]
- Todd, G.C., Griffing, W.J., Gibson, W.R., and Morton, D.M. (1979). Animal models forthe comparative assessment of neurotoxicity following repeated administration of vinca alkaloids. Cancer Treat Rep 63, 35—41.[Web of Science][Medline]
[Order article via Infotrieve]
- Verweij, J., Sparreboom, A., and Nooter, K. (1999). Mitomycins. Cancer Chemother Biol Response Modif 18, 46—58.[Medline]
[Order article via Infotrieve]
- Wang, L.G., Liu, X.M., Kreis, W., and Budman, D.R. (1999). The effect of antimicrotubule agents on signal transduction pathways of apoptosis: a review. Cancer Chemother Pharmacol 44, 355—61.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Wilson, K.C., and Raisman, G. (1980). Age-related changes in the neurosensory epithelium of the mouse vomeronasal organ: extended period of postnatal growth in size and evidence for rapid cell turnover in the adult. Brain Res 185, 103—13.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Yaku, Y., and Saruta, T. (1986). Ultrastructural studies of the olfactory epithelium following bulbectomy evidence of neuronal regeneration. Nippon Jibiinkoka Gakkai Kaiho 89, 1777—86.[Medline]
[Order article via Infotrieve]
- Zhou, X.J., and Rahmani, R. (1992). Preclinical and clinical pharmacology of vinca alkaloids. Drugs 44, 1—16.[Web of Science][Medline]
[Order article via Infotrieve]
Toxicologic Pathology, Vol. 32, No. 6,
701-709 (2004)
DOI: 10.1080/01926230490524283
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
A. M. Jeffrey, M. J. Iatropoulos, and G. M. Williams
Nasal Cytotoxic and Carcinogenic Activities of Systemically Distributed Organic Chemicals
Toxicol Pathol,
December 1, 2006;
34(7):
827 - 852.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
