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Cyclin D1 induced apoptosis maintains the integrity of the G1/S checkpoint following ionizing radiation irradiation

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Somatic Cell and Molecular Genetics

Abstract

Cell cycle “checkpoints” help to ensure the integrity of normal cellular functions prior to replicative DNA synthesis and/or cell division. Cell kinetic abnormalities, particularly arrests at the G1/S and G2/M cell cycle checkpoints, are induced following exposure to ionizing radiationin vitro. Following irradiation, cellular signaling pathways may lead to G1 arrest and/or apoptosis at the G1/S cell cycle transition point. Transfection of cyclin D1, a G1/S cyclin, into a rat embryo cells (REC) results in cellular populations that overexpress cyclin D1, are transformed morphologically, demonstrate an increased incidence of apoptosis, and are tumorigenic in immune-deficient mice. Despite such phenotypic changes, transfected cell populations maintain the itegrity of the G1 checkpoint following ionizing radiation. The transfected cells overexpressing Cyclin D1 have a statistically significant increase in the incidence of apoptosis as compared to parental REC strains or mock-transfected REC. The work provides further evidence of Cyclin D1 playing a critical role in maintaining the integrity of the G1/S checkpoint, via the activation of apoptotic pathways following exposure to ionizing radiationin vitro.

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Abbreviations

REC:

ratembryo cell

Cy D1:

pop, cyclin D1-transfected cell population

pMMTVPRAD-1:

cyclin D1 expression vector

pCMV:

neo, neomycin expression vectoi

cGy:

centigray (1 rad)

Gy:

Gray (100 rad)

MID, SCID:

Severe Combined Immunodeficiency mice; nu/nu. nude mice

NIH III:

triple deficient mice

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Authors and Affiliations

  1. Laboratory of Molecular/Tumor Radiation Biology Mass Gen. Hosp/Harvard Medical School, Tufts University Boston, Massachusetts

    Francisco S. Pardo & Mei Su

  2. Department Community Health, Tufts University Boston, Massachusetts

    Carmia Borek

Authors
  1. Francisco S. Pardo
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  2. Mei Su
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  3. Carmia Borek
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Pardo, F.S., Su, M. & Borek, C. Cyclin D1 induced apoptosis maintains the integrity of the G1/S checkpoint following ionizing radiation irradiation. Somat Cell Mol Genet 22, 135–144 (1996). https://doi.org/10.1007/BF02369903

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  • DOI: https://doi.org/10.1007/BF02369903

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