Mitochondrial ROS and radiation induced transformation in mouse embryonic fibroblasts

Changbin Du; Zhen Gao; Venkatasubbaiah A Venkatesha; Amanda L Kalen; Leena Chaudhuri; Douglas R Spitz; Joseph J Cullen; Larry W Oberley; Prabhat C Goswami

doi:10.4161/cbt.8.20.9648

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Mitochondrial ROS and radiation induced transformation in mouse embryonic fibroblasts

Journal article

Open access

Peer reviewed

Mitochondrial ROS and radiation induced transformation in mouse embryonic fibroblasts

Changbin Du, Zhen Gao, Venkatasubbaiah A Venkatesha, Amanda L Kalen, Leena Chaudhuri, Douglas R Spitz, Joseph J Cullen, Larry W Oberley and Prabhat C Goswami

Cancer biology & therapy, Vol.8(20), pp.1962-1971

10/2009

DOI: 10.4161/cbt.8.20.9648

PMCID: PMC2795790

PMID: 19738419

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Abstract

Manganese superoxide dismutase (SOD2) is a nuclear encoded and mitochondria localized antioxidant enzyme that converts mitochondria derived superoxide to hydrogen peroxide. This study investigates the hypothesis that mitochondria derived reactive oxygen species (ROS) regulate ionizing radiation (IR) induced transformation in normal cells. Mouse embryonic fibroblasts (MEFs) with wild type SOD2 (+/+), heterozygous SOD2 (+/−), and homozygous SOD2 (−/−) genotypes were irradiated with equitoxic doses of IR, and assayed for transformation frequency, cellular redox environment, DNA damage, and cell cycle checkpoint activation. Transformation frequency increased (~ 5-fold) in SOD2 (−/−) compared to SOD2 (+/+) MEFs. Cellular redox environment (GSH, GSSG, DHE, and DCFH-oxidation) did not show any significant change within 24h post-IR. However, a significant increase in cellular ROS levels was observed at 72h post-IR in SOD2 (−/−) compared to SOD2 (+/+) MEFs, which was consistent with an increase in GSSG in SOD2 (−/−) MEFs. Late ROS accumulation was associated with an increase in micronuclei frequency in SOD2 (−/−) MEFs. Exit from G 2 was accelerated in irradiated SOD2 (+/−) and SOD2 (−/−) compared to SOD2 (+/+) MEFs. These results support the hypothesis that SOD2 activity and mitochondria generated ROS regulate IR induced transformation in mouse embryonic fibroblasts.

γ-H2AX

radiation

mitochondria

ROS

SOD2

transformation

micronuclei

G2-checkpoint

Details

Title: Subtitle: Mitochondrial ROS and radiation induced transformation in mouse embryonic fibroblasts
Creators: Changbin Du - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
Zhen Gao - Nevada Cancer Center, Los Vegas, Nevada
Venkatasubbaiah A Venkatesha - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
Amanda L Kalen - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
Leena Chaudhuri - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
Douglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
Joseph J Cullen - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
Larry W Oberley - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
Prabhat C Goswami - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Cancer biology & therapy, Vol.8(20), pp.1962-1971
DOI: 10.4161/cbt.8.20.9648
PMID: 19738419
PMCID: PMC2795790
ISSN: 1538-4047
eISSN: 1555-8576
Language: English
Date published: 10/2009
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984047694802771

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