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Toxicologic Pathology
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Histopathological Study on the PTHrP-Induced Incisor Lesions in Rats

Atsuhiko Kato

Toxicology Laboratory, Chugai Pharmaceutical Co, Ltd, 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan, katoath{at}chugai-pharm.co.jp

Masami Suzuki

Toxicology Laboratory, Chugai Pharmaceutical Co, Ltd, 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan

Yayoi Karasawa

Toxicology Laboratory, Chugai Pharmaceutical Co, Ltd, 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan

Tetsuro Sugimoto

Toxicology Laboratory, Chugai Pharmaceutical Co, Ltd, 1-135 Komakado, Gotemba-shi, Shizuoka 412-8513, Japan

Kunio Doi

Department of Veterinary Pathology, Faculty of Agriculture, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). The present study elucidates the histopathological characters of incisor lesions in the HHM rat model. Nude rats were implanted with PTHrP-expressing tumor (LC-6) cells, maintained for 12 weeks, after which the mandibular incisors were collected. Incisor fractures were observed grossly. Microscopically, hypercalcified dentin, dentin niche with osteodentin, and thinning of dentin were observed. Hypercalcified dentin was observed as a basophilic line of calcified dentin without associated odontoblastic changes, whereas dentin niche and thinning of dentin occurred with osteodentin and loss of cell height, respectively. In contrast with hypercalcified dentin, which was distributed throughout the dentin, dentin niche and thinning of dentin were localized to the labial area of the apical and middle region, and to the labial and lingual areas of the middle and incisal region, respectively. These results suggest that hypercalcemia affected the entire calcification process resulting in hypercalcified dentin, and that high PTHrP concentrations affected selective populations of odontoblasts resulting in formation of dentin niche and thinning of dentin. The localization of dentin niche and thinning of dentin also suggest that PTHrP may also be involved odontoblastic development in the rat.

Key Words: PTHrP • HHM model • tooth lesions • incisor fracture • dentinal lesion • odontoblast • LC-6.

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Toxicologic Pathology, Vol. 31, No. 5, 480-485 (2003)
DOI: 10.1080/01926230390224665
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 Toxicol PatholHome page
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