Investigation of initial changes in the mouse olfactory epithelium following a single intravenous injection of vincristine sulphate.
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.
Kai
Kiyonori
K
Daiichi Pharmaceutical Co. Ltd., Tokyo, Japan. kaikitrx@daiichipharm.co.jp
Yoshida
Mitsuyoshi
M
Sugawara
Tadaki
T
Kato
Michiyuki
M
Uchida
Kazuyuki
K
Yamaguchi
Ryoji
R
Tateyama
Susumu
S
Furuhuma
Kazushisa
K
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001370:Axonal Transport / Q000187:drug effects; D001973:Bromodeoxyuridine; D003952:Diagnostic Imaging; D020287:In Situ Nick-End Labeling; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008938:Mitosis / Q000187:drug effects; D009830:Olfactory Bulb / Q000378:metabolism / Q000502:physiology; D009831:Olfactory Mucosa / Q000378:metabolism / Q000473:pathology*; D014750:Vincristine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*
D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D001973:Bromodeoxyuridine