title: Cell cycle proteins in normal and chemically induced abnormal secondary palate development: a review.
abstract: Cell cycle progression and thus proper cell number is essential for normal development of organs and organisms. Craniofacial tissues including the secondary palate are vulnerable to disruption of cell cycle progression and proliferation by many chemicals including mycotoxin, secalonic acid D (SAD), glucocorticoids, retinoic acid and 2,3,7,8-tetrachlorodibenzodioxin. Induction of cleft palate (CP) by SAD in mice occurs from a reduction in the size of developing palatal shelves. This is associated with an inhibition of proliferation of murine and human embryonic palatal mesenchymal (MEPM and HEPM) cells as well as a G1/S block of cell cycle. In murine embryonic palates and HEPM cells, SAD inhibited G1/S-phase-specific cyclin-dependent kinase (CDK)2 activity, reduced the level of cyclin E and increased the level of the CDK2 inhibitor, p21. These results, together with those from other laboratories, suggest that common cell cycle protein targets (biomarkers), relevant to the pathogenesis of CP by multiple chemical exposures, that can form the basis for the diagnosis and the development of preventive strategies, are likely to exist.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Vamsidhara C
authors.initials: VC
authors.lastname: Dhulipala
authors.forename: Wade V
authors.initials: WV
authors.lastname: Welshons
authors.forename: Chada S
authors.initials: CS
authors.lastname: Reddy
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002972:Cleft Palate / Q000209:etiology / Q000378:metabolism*; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology; D006801:Humans; D010159:Palate / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism*; D013723:Teratogens / Q000633:toxicity
chemical_list: D018797:Cell Cycle Proteins; D013723:Teratogens