Cytotoxicity of 5-aza-2'-deoxycytidine in a mammalian cell system. 1992

S Davidson, and P Crowther, and J Radley, and D Woodcock
Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia.

After the addition of 5-aza-2'-deoxycytidine, a potent inhibitor of DNA methylation and S-phase-specific cytotoxic agent, metaphase chromosomes of Chinese hamster ovary (CHO) cells exhibited a highly decondensed and extended morphology (numerous "fragile sites") at the first mitotic division. However, when a lethal dose of this drug was added in early G1 phase to cells synchronised by mitotic selection, the majority subsequently divided at the same time as an untreated control cell population with few division abnormalities and with few of the more usual types of chromosome aberrations such as gaps, breaks and exchanges. The drug-treated cells also entered and completed the second S-phase without significant delay and it was only at the second mitosis after addition of 5-azadeoxycytidine that cells showed delays in entering mitosis and significant increases in abnormal divisions concomitant with a modest increase in chromosome aberrations. If cells in a tumour behave similarly, the tumour mass would be expected to double before any reduction in tumour burden could be expected to occur.

UI MeSH Term Description Entries
D008745 Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed) Methylations
D010053 Ovary The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE. Ovaries
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002869 Chromosome Aberrations Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS. Autosome Abnormalities,Cytogenetic Aberrations,Abnormalities, Autosome,Abnormalities, Chromosomal,Abnormalities, Chromosome,Chromosomal Aberrations,Chromosome Abnormalities,Cytogenetic Abnormalities,Aberration, Chromosomal,Aberration, Chromosome,Aberration, Cytogenetic,Aberrations, Chromosomal,Aberrations, Chromosome,Aberrations, Cytogenetic,Abnormalities, Cytogenetic,Abnormality, Autosome,Abnormality, Chromosomal,Abnormality, Chromosome,Abnormality, Cytogenetic,Autosome Abnormality,Chromosomal Aberration,Chromosomal Abnormalities,Chromosomal Abnormality,Chromosome Aberration,Chromosome Abnormality,Cytogenetic Aberration,Cytogenetic Abnormality
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005260 Female Females
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000077209 Decitabine An azacitidine derivative and antineoplastic antimetabolite. It inhibits DNA methyltransferase to re-activate silent genes, limiting METASTASIS and NEOPLASM DRUG RESISTANCE. Decitabine is used in the treatment of MYELODISPLASTIC SYNDROMES, and ACUTE MYELOID LEUKEMIA. 2'-Deoxy-5-azacytidine,5-Aza-2'-deoxycytidine,5-AzadC,5-Azadeoxycytidine,5-Deoxyazacytidine,5AzadC,AzadC Compound,Dacogen,Decitabine Mesylate,NSC 127716,NSC-127716,2' Deoxy 5 azacytidine,5 Aza 2' deoxycytidine,5 Azadeoxycytidine,5 Deoxyazacytidine,Compound, AzadC,Mesylate, Decitabine,NSC127716

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