BIOMAT Database Logo BIOMAT Database Logo

Delayed apoptotic responses associated with radiation-induced neoplastic transformation of human hybrid cells. 1999

M S Mendonca, and K L Howard, and D L Farrington, and L A Desmond, and T M Temples, and B M Mayhugh, and J J Pink, and D A Boothman
Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis 46202, USA.

HeLa X human skin fibroblast hybrid cells have been developed into a model for radiation-induced neoplastic transformation of human cells. Previous studies indicate that the appearance of neoplastically transformed foci in this system is delayed for several population doublings after irradiation and appears to involve the loss of putative tumor suppressor loci on fibroblast chromosomes 11 and 14. We now show that after treatment with 7 Gy of X-rays, transformed foci initiation correlates with delayed apoptosis initiated in the progeny of the irradiated cells after 10-12 cell divisions and with reduced plating efficiency (delayed death). The cells develop classic apoptotic morphology, positive terminal deoxynucleotidyl transferase-mediated nick end labeling and phosphatidylserine (annexin V) staining, and cleavage of poly(ADP-ribose) polymerase. In addition, a delayed induction of the p53 protein and the proapoptotic Bax protein is evident over a week after radiation exposure. We propose that a delayed build-up of mitosis-dependent genomic DNA damage or a loss of genetic material over time (10-12 cell divisions postirradiation) has two relevant outcomes: (a) cell death due to the delayed induction of a p53-dependent apoptosis; and (b) neoplastic transformation of a minor subset of survivors that has lost fibroblast chromosomes 11 and 14 (tumor suppressor loci for this system) and has either evaded apoptosis or not acquired enough genetic damage to induce apoptosis. It is postulated that both phenomena result from X-ray-induced, translesion-mediated genomic instability.

UI MeSH Term Description Entries
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
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006822 Hybrid Cells Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION. Somatic Cell Hybrids,Cell Hybrid, Somatic,Cell Hybrids, Somatic,Cell, Hybrid,Cells, Hybrid,Hybrid Cell,Hybrid, Somatic Cell,Hybrids, Somatic Cell,Somatic Cell Hybrid
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis

Related Publications

M S Mendonca, and K L Howard, and D L Farrington, and L A Desmond, and T M Temples, and B M Mayhugh, and J J Pink, and D A Boothman
Delayed heritable damage and epigenetics in radiation-induced neoplastic transformation of human hybrid cells.
May 1993, Radiation research,
M S Mendonca, and K L Howard, and D L Farrington, and L A Desmond, and T M Temples, and B M Mayhugh, and J J Pink, and D A Boothman
Radiation-induced neoplastic transformation of human cells.
March 1993, Scanning microscopy,
M S Mendonca, and K L Howard, and D L Farrington, and L A Desmond, and T M Temples, and B M Mayhugh, and J J Pink, and D A Boothman
Evidence for a role of delayed death and genomic instability in radiation-induced neoplastic transformation of human hybrid cells.
December 1998, International journal of radiation biology,
M S Mendonca, and K L Howard, and D L Farrington, and L A Desmond, and T M Temples, and B M Mayhugh, and J J Pink, and D A Boothman
Radiation-induced neoplastic transformation of human prostate epithelial cells.
January 1996, Cancer research,
M S Mendonca, and K L Howard, and D L Farrington, and L A Desmond, and T M Temples, and B M Mayhugh, and J J Pink, and D A Boothman
A radiation-induced acute apoptosis involving TP53 and BAX precedes the delayed apoptosis and neoplastic transformation of CGL1 human hybrid cells.
June 2005, Radiation research,
M S Mendonca, and K L Howard, and D L Farrington, and L A Desmond, and T M Temples, and B M Mayhugh, and J J Pink, and D A Boothman
Neoplastic transformation of human hybrid cells by gamma radiation: a quantitative assay.
June 1987, Radiation research,
M S Mendonca, and K L Howard, and D L Farrington, and L A Desmond, and T M Temples, and B M Mayhugh, and J J Pink, and D A Boothman
Mechanisms of radiation-induced neoplastic transformation of human bronchial epithelial cells.
January 2001, Radiation research,
M S Mendonca, and K L Howard, and D L Farrington, and L A Desmond, and T M Temples, and B M Mayhugh, and J J Pink, and D A Boothman
Ultraviolet radiation-induced neoplastic transformation of normal human cells, in vitro.
July 1981, Chemico-biological interactions,
M S Mendonca, and K L Howard, and D L Farrington, and L A Desmond, and T M Temples, and B M Mayhugh, and J J Pink, and D A Boothman
Cytoskeletal changes during radiation-induced neoplastic transformation of human prostate epithelial cells.
January 1996, Scanning microscopy,
M S Mendonca, and K L Howard, and D L Farrington, and L A Desmond, and T M Temples, and B M Mayhugh, and J J Pink, and D A Boothman
Production of delayed death and neoplastic transformation in CGL1 cells by radiation-induced bystander effects.
September 2001, Radiation research,
Copied contents to your clipboard!