Species and sex differences in susceptibility to olfactory lesions among the mouse, rat and monkey following an intravenous injection of vincristine sulphate.

Species and sex differences in susceptibility to vincristine sulphate (VCR)-induced olfactory epithelial lesions were investigated among the BALB/c mice, Crj: CD(SD) IGS rats and common marmoset monkeys following a single intravenous administration on day 1. As dosage levels, the 0.17-fold LD10, 0.

Olfactory epithelial lesions induced by various cancer chemotherapeutic agents in mice.

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 (LD(10)) 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 LD(10) of PTX or 5-FU.

Olfactory epithelium as a novel toxic target following an intravenous administration of vincristine to mice.

To delineate morphological characteristics of olfactory lesions induced by vincristine (VCR), a vinca alkaloid derivative with antitumor activity, male BALB/c mice were given a single intravenous injection of 1.95 mg/kg, an estimated 10% lethal dose (designated as day 1). The animals were serially sacrificed on days 2, 3, 5, 10, 15 and 60, and the nasal mucosa was examined histopathologically.