Thymidine kinase, DNA synthesis and cancer. 1976

S Kit

A resume has been presented of some recent investigations which show that DNA synthesis can be initiated in many types of quiescent animal cells by external stimuli, by introducing a quiescent nucleus into the cytoplasm of a proliferating cell, or by a virus infection. The components of the DNA replication apparatus are described. It is shown that deoxyribonucleoside triphosphate pools increase substantially in animal cells at the time DNA synthesis is initiated due to the enhanced activities of enzymes functioning in nucleotide synthesis. Especially striking is the increase of thymidine kinase activity, indicating that this enzyme may be a useful marker of the shift from the quiescent to the replicative state. The thymidine kinase isozymes of vertebrate cells have been characterized. Thymidine kinase F, which is found principally in the cytosol, is the isozyme that increases when G1 (Go) phase cells are stimulated or infected with oncogenic viruses. Chick cytosol thymidine kinase F can also be reactivated by introducing differentiated chick erythrocyte nuclei into the cytoplasm of enzyme-deficient LM (TK-) mouse cells. Furthermore, herpesviruses code for distinctive, virus-specific thymidine kinase isozymes, so that another way to transform thymidine kinase-deficient LM TK-) cells to kinase-positive cells is by infecting them with UV-irradiated herpes simplex viruses. The experiments on the activation of DNA synthesis and thymidine kinase F activity have been discussed in the context of the proliferative activity in vivo and the immortalization in culture of neoplastic cells. These experiments suggest that genes determining cell cycle proteins are readily accessible to transcription and translation in essentially all nucleated cells. The tendency of transformed cells to become multinucleated after cytochaliasin B treatment also suggests that one important difference between malignant cells and most normal cells may be the ability of malignant cells to 'stockpile' the proteins (and/or their messenger RNAs) of the DNA replicative apparatus and to maintain the 'stockpiles' in progeny cells.

UI MeSH Term Description Entries
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D001973 Bromodeoxyuridine A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. BUdR,BrdU,Bromouracil Deoxyriboside,Broxuridine,5-Bromo-2'-deoxyuridine,5-Bromodeoxyuridine,NSC-38297,5 Bromo 2' deoxyuridine,5 Bromodeoxyuridine,Deoxyriboside, Bromouracil
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D003600 Cytosol Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components. Cytosols
D004261 DNA Replication The process by which a DNA molecule is duplicated. Autonomous Replication,Replication, Autonomous,Autonomous Replications,DNA Replications,Replication, DNA,Replications, Autonomous,Replications, DNA
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA

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