Cyclophosphamide inhibits root development of molar teeth in growing mice. 2015

Tomomi Kawakami, and Yuko Nakamura, and Hiroyuki Karibe
Department of Pediatric Dentistry, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20, Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan, tomomi-k@tky.ndu.ac.jp.

Root development of permanent teeth is disturbed in survivors of childhood cancer. Cyclophosphamide (CY) is a cytostatic drug commonly used for chemotherapy in children with cancer. This study aimed to evaluate the effects of CY on the development of molar teeth until the completion of occlusion in young mice, focusing on Hertwig's epithelial root sheath (HERS). We treated thirty-two 12-day-old ICR mice with CY (100 mg/kg; 100-CY group), and 36 control mice with saline. At 12, 14, 16, 20, 24, 27, 39, 60, and 76 days of age, the mandibular molars were removed. Soft X-ray radiographs were obtained in lateral projection. The root/crown length (R/C) ratio of the first molar was calculated. Serial sagittal sections were prepared and histomorphological hematoxylin and eosin (HE) staining and immunohistochemical (cytokeratin) studies were performed. The R/C ratio of the 100-CY group (0.78) was smaller than that of the control group (1.23) at 76 days (p < 0.05, t test). While all roots developed further after injection, microscopic examination showed that the roots of the first molars that developed in the 100-CY group were shorter than those in the control group. In addition, experimental mice showed apical closure of the roots. By 20 days after injection, the HERS had disappeared from the root surface in the 100-CY group. In conclusion, this study indicates that CY can induce a defect in HERS and cause early loss of HERS. Disruption of the epithelial sheath inhibits normal root formation, and it could cause irreversible short-root development.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008813 Mice, Inbred ICR An inbred strain of mouse that is used as a general purpose research strain, for therapeutic drug testing, and for the genetic analysis of CARCINOGEN-induced COLON CANCER. Mice, Inbred ICRC,Mice, ICR,Mouse, ICR,Mouse, Inbred ICR,Mouse, Inbred ICRC,ICR Mice,ICR Mice, Inbred,ICR Mouse,ICR Mouse, Inbred,ICRC Mice, Inbred,ICRC Mouse, Inbred,Inbred ICR Mice,Inbred ICR Mouse,Inbred ICRC Mice,Inbred ICRC Mouse
D008963 Molar The most posterior teeth on either side of the jaw, totaling eight in the deciduous dentition (2 on each side, upper and lower), and usually 12 in the permanent dentition (three on each side, upper and lower). They are grinding teeth, having large crowns and broad chewing surfaces. (Jablonski, Dictionary of Dentistry, 1992, p821) Molars
D003520 Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. (+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate,B-518,Cyclophosphamide Anhydrous,Cyclophosphamide Monohydrate,Cyclophosphamide, (R)-Isomer,Cyclophosphamide, (S)-Isomer,Cyclophosphane,Cytophosphan,Cytophosphane,Cytoxan,Endoxan,NSC-26271,Neosar,Procytox,Sendoxan,B 518,B518,NSC 26271,NSC26271
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014092 Tooth Root The part of a tooth from the neck to the apex, embedded in the alveolar process and covered with cementum. A root may be single or divided into several branches, usually identified by their relative position, e.g., lingual root or buccal root. Single-rooted teeth include mandibular first and second premolars and the maxillary second premolar teeth. The maxillary first premolar has two roots in most cases. Maxillary molars have three roots. (Jablonski, Dictionary of Dentistry, 1992, p690) Root, Tooth,Roots, Tooth,Tooth Roots
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular

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