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Cell cycle proteins in normal and chemically induced abnormal secondary palate development: a review

Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

Wade V Welshons

Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA

Chada S Reddy

Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA; reddyc{at}missouri.edu

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.

Key Words: cell cycle • cleft palate • cyclins • cyclin-dependent kinases • cyclin-dependent kinase inhibitors • secalonic acid D

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Human & Experimental Toxicology, Vol. 25, No. 11, 675-682 (2006)
DOI: 10.1177/0960327106070848


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Dhulipala, V. C Articles by Reddy, C. S Search for Related Content PubMed PubMed Citation Articles by Dhulipala, V. C Articles by Reddy, C. S Pubmed/NCBI databases Medline Plus Health Information Cleft Lip and Palate Head and Brain Malformations Social Bookmarking                         What's this?