title: Histopathological study of time course changes in PTHrP-induced incisor lesions of rats.
abstract: Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). In the present study using HHM model rats, the time course of odontoblastic response to PTHrP and its relation to incisal fracture were elicited. Nude rats were implanted with PTHrP-expressing tumor (LC-6) cells, mandibular incisors were collected at several time points. Microscopically 3 distinctive types of odontoblastic/dentin lesions were observed. Hypercalcfied dentin, which was reported as hypercalcemia-induced lesion in previous reports, observed in all areas of the dentin from week 5-10 samplings. Dentin niche, observed solely in week-10 sampling point, exhibited a nature identical to that of reparative odontoblast reported in the literatures of various cytotoxic agents. Since cytotoxicites were neither observed prior to the lesions nor reported as a role of PTHrP, the reparative response may have derived from highly sustained levels of PTHrP. Loss of columnar odontoblasts height was initially observed at week-5 time point in the middle section of the incisor. This primary loss of cell height prior to incisor fracture was considered to be the earliest response to the increased PTHrP levels of this model.
authors.affiliation: Toxicology Laboratory, Chugai Pharmaceutical Co., Ltd., Gotemba-shi, Shizuoka 412-8513, Japan. katoath@chugai-pharm.co.jp
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kato
authors.forename: Masami
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Karasawa
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Kunio
authors.initials: K
authors.lastname: Doi
mesh_terms: D000818:Animals; D002118:Calcium / Q000097:blood; D045744:Cell Line, Tumor; D003804:Dentin / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007180:Incisor / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008334:Mandible; D051379:Mice; D009368:Neoplasm Transplantation; D009804:Odontoblasts / Q000378:metabolism / Q000473:pathology*; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D051381:Rats; D011923:Rats, Nude; D013997:Time Factors
chemical_list: D044162:Parathyroid Hormone-Related Protein; D002118:Calcium