Importance of DNA damage in the induction of apoptosis by ionizing radiation: effect of the scid mutation and DNA ploidy an the radiosensitivity of murine lymphoid cell lines
Details
Publication Year 1999-02,Volume 75,Issue #2,Page 143-153
Journal Title
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
Publication Type
Journal Article
Abstract
Purpose: To study the effects of the murine scid mutation and DNA ploidy on the susceptibility of lymphoid cell lines to induction of apoptosis by ionizing radiation and thereby to determine whether DNA lesions are critical initiators of apoptosis. Materials and methods: Sensitivity to killing and rapidity of induction of apoptosis following gamma-irradiation or DNA-associated I-125 decays were compared in pre-B and pre-T cell lines derived from wild-type mice and from mice homozygous or heterozygous for the scid mutation, Effects of differences in DNA ploidy on the same endpoints were studied using pseudo-diploid and -tetraploid clones of a murine pre-T cell line. Results: Pairs of pre-B- and pre-T cell-derived lines that expressed wild-type p53 and underwent rapid interphase apoptosis after irradiation were identified. In both cases, the scid homozygous cell lines were more sensitive to killing, suggesting that DNA repair capability influences susceptibility to induction of apoptosis, Increasing DNA ploidy in a cell line that undergoes rapid interphase apoptosis produced a corresponding increase in the number of DNA lesions required to produce a lethal event; again consistent with DNA being the target for radiation action. Conclusion: DNA damage is an important, if not the sole, initiator of external beam ionizing radiation-induced apoptosis.
Publisher
TAYLOR & FRANCIS LTD
Keywords
DEPENDENT PROTEIN-KINASE; STRAND BREAK REPAIR; COMBINED IMMUNE-DEFICIENCY; POLYMERASE CHAIN-REACTION; V(D)J RECOMBINATION; INCREASED SENSITIVITY; TYROSINE KINASE; ALPHA-PARTICLES; P53 MUTATIONS; MOUSE
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Creation Date: 1999-02-01 12:00:00
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