Delayed lethality, apoptosis and micronucleus formation in human fibroblasts irradiated with X-rays or alpha-particles. 1999

O V Belyakov, and K M Prise, and K R Trott, and B D Michael
Gray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, UK.

OBJECTIVE To determine the yields of cell lethality and micronucleus formation measured immediately after irradiation or at delayed times in primary human fibroblasts exposed to X-rays or alpha-particles. METHODS Primary human AG01522B fibroblasts were irradiated with X-rays or alpha-particles and subcultured for up to 30 days post-irradiation. Clonogenic survival and the yield of micronucleated cells in newly divided daughter cells were scored at various times. RESULTS After the initial dose-dependent acute response for both endpoints there was conclusive evidence for the delayed production of de novo genomic instability in the surviving progeny. As well as the production of micronucleated cells, evidence was observed for the production of fibroblasts undergoing apoptosis as measured using conventional morphological scoring, 3'OH end-labelling of DNA fragmentation and externalization of phosphatidyl serine residues to the cell surface. For both radiations, the dose and time dependencies of the apoptotic response were similar to those for micronucleation and loss of clonogenicity. CONCLUSIONS Genomic instability in the progeny of irradiated primary human fibroblasts was observed in the form of micronucleation, apoptosis and delayed reproductive death. An increased effectiveness of alpha-particles versus X-rays was observed for both initial and delayed responses, including apoptosis.

UI MeSH Term Description Entries
D010718 Phosphatidylserines Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a SERINE moiety. Serine Phosphoglycerides,Phosphatidyl Serine,Phosphatidyl Serines,Phosphatidylserine,Phosphoglycerides, Serine,Serine, Phosphatidyl,Serines, Phosphatidyl
D011829 Radiation Dosage The amount of radiation energy that is deposited in a unit mass of material, such as tissues of plants or animal. In RADIOTHERAPY, radiation dosage is expressed in gray units (Gy). In RADIOLOGIC HEALTH, the dosage is expressed by the product of absorbed dose (Gy) and quality factor (a function of linear energy transfer), and is called radiation dose equivalent in sievert units (Sv). Sievert Units,Dosage, Radiation,Gray Units,Gy Radiation,Sv Radiation Dose Equivalent,Dosages, Radiation,Radiation Dosages,Units, Gray,Units, Sievert
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000512 Alpha Particles Positively charged particles composed of two protons and two NEUTRONS, i.e. equivalent to HELIUM nuclei, which are emitted during disintegration of heavy ISOTOPES. Alpha rays have very strong ionizing power, but weak penetrability. Alpha Rays,Alpha Radiation,Radiation, Alpha,Alpha Particle,Alpha Ray,Particle, Alpha,Particles, Alpha,Ray, Alpha,Rays, Alpha
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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