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Modulation of Radiation responses by pre-exposure to irradiated Cell conditioned medium.
Maguire, Paula Mothersill, Carmel McClean, Brendan Seymour, Colin Lyng, Fiona M
Maguire, Paula
Mothersill, Carmel
McClean, Brendan
Seymour, Colin
Lyng, Fiona M
Advisors
Editors
Other Contributors
Departments
Date
2007-04
Date Submitted
Keywords
HUMAN PAPILLOMA VIRUS
NEOPLASMS
CANCER
RADIOTHERAPY
NEOPLASMS
CANCER
RADIOTHERAPY
Other Subjects
Subject Mesh
Adaptation, Physiological
Cell Line
Cell Survival
Culture Media, Conditioned
DNA
DNA Damage
Dose-Response Relationship, Radiation
Humans
Keratinocytes
Radiation Dosage
Radiation Tolerance
Cell Line
Cell Survival
Culture Media, Conditioned
DNA
DNA Damage
Dose-Response Relationship, Radiation
Humans
Keratinocytes
Radiation Dosage
Radiation Tolerance
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
Abstract
The aim of this study was to investigate whether exposure of HPV-G cells to irradiated cell conditioned medium (ICCM) could induce an adaptive response if the cells were subsequently challenged with a higher ICCM dose. Clonogenic survival and major steps in the cascade leading to apoptosis, such as calcium influx and loss of mitochondrial membrane potential, were examined to determine whether these events could be modified by giving a priming dose of ICCM before the challenge dose. Clonogenic survival data indicated an ICCM-induced adaptive response in HPV-G cells "primed" with 5 mGy or 0.5 Gy ICCM for 24 h and then exposed to 0.5 Gy or 5 Gy ICCM. Reactive oxygen species (ROS) were found to be involved in the bystander-induced cell death. Calcium fluxes varied in magnitude across the exposed cell population, and a significant number of the primed HPV-G cells did not respond to the challenge ICCM dose. No significant loss of mitochondrial membrane potential was observed when HPV-G cells were exposed to 0.5 Gy ICCM for 24 h followed by exposure to 5 Gy ICCM for 6 h. Exposure of HPV-G cells to 5 mGy ICCM for 24 h followed by exposure to 0.5 Gy ICCM for 18 h caused a significant increase in mitochondrial mass and a change in mitochondrial location, events associated with the perpetuation of genomic instability. This study has shown that a priming dose of ICCM has the ability to induce an adaptive response in HPV-G cells subsequently exposed to a challenge dose of ICCM.
Language
en
ISSN
0033-7587
eISSN
ISBN
DOI
10.1667/RR0159.1
PMID
17388689