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Toxicologic Pathology
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Articles

Investigation of Initial Changes in the Mouse Olfactory Epithelium Following a Single Intravenous Injection of Vincristine Sulphate

Kiyonori Kai1
Mitsuyoshi Yoshida1
Tadaki Sugawara1
Michiyuki Kato1
Kazuyuki Uchida2
Ryoji Yamaguchi2
Susumu Tateyama2
Kazushisa Furuhuma1

1 Daiichi Pharmaceutical Co. Ltd., Tokyo, Japan
2 Miyazaki University, Department of Veterinary Faculty of Agriculture, Tokyo, Japn

Correspondence: Address correspondence to: Kiyonoir Kai, Daiichi Pharmaceutical Co., Ltd., Drug Safety Research Laboratory, 1-16-13, Kita-Kasai, Edogawaku Tokyo 134-8630, Japan; e-mail:kaikitrx{at}daiichipharm.co.jp

To investigate initial changes in the olfactory epithelium, vincristine sulphate (VCR) was administered intravenously once to male BALB/c mice on day 1 in comparison with unilateral bulbectomy (UBT). The light and electron microscopy of the olfactory epithelium, nerve and/or bulb with BrdU-morphometry was performed sequentially. Further, whole-body radioluminography was conducted at 1 and 24 hours postdose. Apoptosis and an increased number of mitotic cells with a tendency toward decreasing BrdU-positive olfactory epithelial cell counts were observed in olfactory epithelial cells at 6 hours postdose of VCR and became more pronounced at 24 hours postdose. These changes disappeared on days 4 or 15, but minimal axonal degeneration was seen in the olfactory nerve from day 4 onward. Semiquantitative measurement of VCR levels in the ethmoturbinals elicited high drug retention even 24 hours after administration. In contrast, UBT showed no effect on mitosis and BrdU-positive cell counts at 6 hours postdose, but severe lesions in the olfactory epithelium and nerve were seen on days 2, 4, and/or 15. The above results suggest that the initial event of VCR-induced apoptosis in the mouse olfactory epithelium would be mitotic arrest with high drug retention, unlike that evoked by UBT.

Key Words: Apoptosis • initial change • mice • olfactory epithelium • vincristine sulphate

Toxicologic Pathology, Vol. 33, No. 7, 752-761 (2005)
DOI: 10.1080/01926230500417045
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