Abstract
DNA damage induced by irradiation causes overexpression of the p53 gene, and subsequently the upregulation of p53 downstream genes involved in cell cycle modification. Irradiated malignant cells which possess wild-type p53 have been known to undergo G1 arrest due to p21/Cip1/Waf1 upregulation. Other p53 downstream genes related to the modification of the cell cycle such as gadd45 may cause G2 arrest. Many of the genes which regulate the cell cycle progression have been identified, including the G1 phase specific ink4 family of cyclin-dependent kinase inhibitors (CDK-I), another group of CDK-Is, which affect the cyclin-CDK complexes ubiquitously, and S/G2 accelerator genes. The sequential changes in these cell cycle regulator genes after irradiation has not been clarified. We analyzed the appearance of the apoptotic fraction and cell cycle perturbation after irradiation using KB, a human squamous cell carcinoma line derived from oral floor, and examined the alteration of gene expression for cell cycle regulator genes. The KB cells proceeded to undergo apoptosis in a time and dose dependent manner after irradiation and showed G2 arrest accompanied by upregulation of p53, ubiquitous CDK-Is, and S and G2 accelerator genes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / genetics
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Apoptosis / radiation effects
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Carcinoma, Squamous Cell / pathology*
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Cell Cycle / genetics
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Cell Cycle / radiation effects
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Cell Cycle Proteins / biosynthesis*
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Cell Cycle Proteins / genetics
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Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases / biosynthesis
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Cyclin-Dependent Kinases / genetics
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Cyclins / biosynthesis
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Cyclins / genetics
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DNA Damage
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DNA, Neoplasm / genetics
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DNA, Neoplasm / radiation effects*
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Fungal Proteins / biosynthesis
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Fungal Proteins / genetics
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G2 Phase / radiation effects
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GADD45 Proteins
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Gene Expression Regulation, Neoplastic / radiation effects*
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Genes, p16
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Genes, p53
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Humans
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Intracellular Signaling Peptides and Proteins
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KB Cells / metabolism
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KB Cells / radiation effects*
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Microtubule-Associated Proteins / biosynthesis
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Microtubule-Associated Proteins / genetics
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Molecular Motor Proteins
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Mouth Neoplasms / pathology*
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Neoplasm Proteins / biosynthesis*
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Neoplasm Proteins / genetics
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Protein Biosynthesis
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Proteins / genetics
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S-Phase Kinase-Associated Proteins
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Saccharomyces cerevisiae Proteins*
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Tumor Suppressor Protein p53 / biosynthesis
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Tumor Suppressor Proteins*
Substances
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CDKN1A protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DNA, Neoplasm
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Fungal Proteins
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Intracellular Signaling Peptides and Proteins
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KIP2 protein, S cerevisiae
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Microtubule-Associated Proteins
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Molecular Motor Proteins
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Neoplasm Proteins
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Proteins
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S-Phase Kinase-Associated Proteins
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Saccharomyces cerevisiae Proteins
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases