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Morphological Classification of Dental Lesions Induced by Various Antitumor Drugs in Mice

Drug Safety Research Laboratory, Daiichi Pharmaceutical Co, Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan, satohe9j{at}daiichipharm.co.jp

Yasuo Uesugi

Drug Safety Research Laboratory, Daiichi Pharmaceutical Co, Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan

Takami Kawabata

Drug Safety Research Laboratory, Daiichi Pharmaceutical Co, Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan

Kazuhiko Mori

Drug Safety Research Laboratory, Daiichi Pharmaceutical Co, Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan

Fumitaka Fuj

Drug Safety Research Laboratory, Daiichi Pharmaceutical Co, Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan

Yoshinori Kashimoto

Drug Safety Research Laboratory, Daiichi Pharmaceutical Co, Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan

Tetsuyo Kajimura

Drug Safety Research Laboratory, Daiichi Pharmaceutical Co, Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan

Kazuhisa Furuhama

Drug Safety Research Laboratory, Daiichi Pharmaceutical Co, Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan

To characterize and compare maxillary incisor lesions caused by various antitumor drugs, male BALB/c mice were given a single intravenous injection of an estimated 10% lethal dose (LD₁₀) of 5-fluorouracil (5-FU), adriamycin (ADR), mitomycin C (MMC), vinblastine sulfate (VBL), taxotere (TXR), irinotecan hydrochloride CPT-11 , DX-8951f, or cisplatin (CDDP). After 3, 5, 10, 15, and 60 days, the animals were sacrificed, and the maxillary incisors were examined microscopically. The dental lesions observed were classified into 4 different types on the basis of their morphological features. The lesion due to 5-FU was characterized by focal defects in the dentin, and this injury was reversible (transient dentin injury). ADR- or MMC-induced lesions were defined by abnormal structure of the apical aspect of the tooth and irregular odontogenesis, lasting for a long period (persistent apical injury). Treatment with VBL or TXR showed irregular enamel formation and abnormal dentinogenesis. Their targets were considered to be both immature and mature odontogenic cells (diffuse dental injury). Exposure to CPT-11, DX-8951f, or CDDP elicited minor reductions in a few precursor cells in the epithelial sheath on day 3, but no prominent dental abnormalities were seen thereafter (nontoxic injury). In conclusion, antitumor drugs can cause a variety of dental lesions that vary temporally and spatially, making histopathological examination of the maxillary incisor an important component of the safety assessment process for novel antitumor drugs.

Key Words: 5-fluorouracil (5-FU) • adriamycin (ADR) • mitomycin C (MMC) • vinblastine sulfate (VBL) • taxotere (TXR) • irinotecan hydrochloride (CPT-11) • DX-8951f • cisplatin (CDDP)

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Toxicologic Pathology, Vol. 29, No. 3, 292-299 (2001)
DOI: 10.1080/019262301316905246


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