Ascorbate as a “redox sensor” and protector against irradiation-induced oxidative stress in 32D CL 3 hematopoietic cells and subclones overexpressing human manganese superoxide dismutase

Epperly, Michael W.; Осипов, А Н; Martin, Ian; Kawai, Kazuaki; Borisenko, Grigory G.; Tyurina, Yulia Y.; Jefferson, Mia; Bernarding, Michael; Greenberger, Joel S.; Kagan, Valerian E.

doi:10.1016/j.ijrobp.2003.10.022

Cited by 35 publications

(44 citation statements)

References 28 publications

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“…Some data point to stabilization of the mitochondrial membrane and a subsequent inhibition of apoptosis as being central to the radioprotective effect [39]. However, SOD2 overexpression is associated with reduced oxidative stress in irradiated cells [25] whilst our data and those of others show that SOD2 also reduces the extent of acute DNA damage induced by ionizing radiation [1]. Such damage is also a powerful signal for the onset of apoptosis.…”

Section: Discussionsupporting

confidence: 57%

“…Plasmid transfection and expression of SOD2 in the murine haematopoietic cell line 32D cl 3 leads to protection of cells against ionizing irradiation induced cell killing through the plasmid driven overexpression of SOD2 [24] mediated by the scavenging of ROS [25]. Here we present data using primary murine bone marrow and the human erythroleukaemic cell line K562 transduced with a retrovirus that is optimized for transcription in haematopoietic cells (SFß91) [26] and which encodes SOD2 and the reporter gene enhanced green fluorescent protein (eGFP).…”

Section: Introductionmentioning

confidence: 99%

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Radioprotective gene therapy through retroviral expression of manganese superoxide dismutase

Southgate

Sheard

Milsom

et al. 2006

The Journal of Gene Medicine

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Radioprotective gene therapy through retroviral expression of manganese superoxide dismutase

Southgate

Sheard

Milsom

et al. 2006

The Journal of Gene Medicine

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“…[9][10][11][12][25][26][27][28][29][30][31] With the availability of sophisticated computer-controlled modification systems for clinical radiotherapy dose distribution by modern linear accelerators including intensity-modulated radiation therapy, 1,2,7 many physical barriers to dose optimization in complex tumor volumes have been overcome. Unfortunately, effective high dose delivery to complex tumor volumes in the thoracic cavity, which has been developed for patients with lung cancer, esophagus cancer, and other thoracic malignancies, has necessitated often large lung transit volumes and associated toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Such a method of lung radiation protection might also be applicable to environmental radiation protection for radiation safety workers, nuclear reactor clean-up personnel, and emergency response personnel working in an area of unanticipated continuous low level of ionizing irradiation contamination. 25 There have been many approaches attempted for designing new modalities for radiation protection. Pharmacologic interventions and biologic response modifiers have recently been focused on pulmonary radiation protection.…”

Section: Discussionmentioning

confidence: 99%

Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage

et al. 2005

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Intratracheal injection of manganese superoxide dismutaseplasmid/liposome (MnSOD-PL) complexes has been demonstrated to delay the onset and reduce the extent of ionizing irradiation-induced murine pulmonary organizing alveolitis/ fibrosis. To facilitate translation of this modality to clinical fractionated radiotherapy, inhalation delivery of MnSOD-PL was developed using an ultrasonic nebulizer. Transgene product was quantitated by immunohistochemical quantitation and pulmonary tissue levels of MnSOD biochemical activity. C57BL/6NHsd female mice demonstrated a plasmid dose-dependent increased expression of MnSOD transgene product over the range of 250 mg-2.5 mg of MnSOD-PL administered over a constant 5 min interval. Delivery of a constant concentration of 500 mg of MnSOD-PL with varying times of administration ranging from 0.5 to 10 min demonstrated optimal MnSOD expression at 5 min. Mice pretreated by inhalation delivery of MnSOD-PL demonstrated significantly improved survival after 20 Gy single fraction irradiation to both lungs compared to LacZ-PL inhalation-treated or irradiated control mice. Mice receiving 10 fractions of 3.5 cGy demonstrated increased pulmonary MnSOD transgene product activity by a protocol of every Monday-Wednesday or daily inhalation of MnSOD-PL. Thus, inhalation radioprotective gene therapy using MnSOD-PL provides a practical and effective method for delivery of lung-specific radioprotection during fractionated radiotherapy protocols in a mouse model. Gene Therapy (2005) 12, 685-693.

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“…In contrast, 2-ME can sensitize radioresistant MCF-7/FIR breast cancer cells by activating apoptosis, arresting the cell cycle, and further enhancing radiation-induced ROS (152). Therefore, applying redoxmodulating reagents, such as ascorbate (49), arsenic trioxide (34), selenite (76), or a metalloporphyrin antioxidant mimetic (MnTE-2-PyP) (112), in combination with IR can either increase the cell-killing effect of IR or protect against radiationinduced oxidative stress to surrounding normal tissues.…”

Section: Radioresistance: An Important Impediment To Prostate Cancer mentioning

confidence: 99%

Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

Liu

Holley

Zhao

et al. 2014

Antioxidants & Redox Signaling

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Significance: Radiation therapy is widely used for treatment of prostate cancer. Radiation can directly damage biologically important molecules; however, most effects of radiation-mediated cell killing are derived from the generated free radicals that alter cellular redox status. Multiple proinflammatory mediators can also influence redox status in irradiated cells and the surrounding microenvironment, thereby affecting prostate cancer progression and radiotherapy efficiency. Recent Advances: Ionizing radiation (IR)-generated oxidative stress can regulate and be regulated by the production of proinflammatory mediators. Depending on the type and stage of the prostate cancer cells, these proinflammatory mediators may lead to different biological consequences ranging from cell death to development of radioresistance. Critical Issues: Tumors are heterogeneous and dynamic communication occurs between stromal and prostate cancer cells, and complicated redox-regulated mechanisms exist in the tumor microenvironment. Thus, antioxidant and anti-inflammatory strategies should be carefully evaluated for each patient at different stages of the disease to maximize therapeutic benefits while minimizing unintended side effects. Future Directions: Compared with normal cells, tumor cells are usually under higher oxidative stress and secrete more proinflammatory mediators. Thus, redox status is often less adaptive in tumor cells than in their normal counterparts. This difference can be exploited in a search for new cancer therapeutics and treatment regimes that selectively activate cell death pathways in tumor cells with minimal unintended consequences in terms of chemo-and radio-resistance in tumor cells and toxicity in normal tissues. Antioxid. Redox Signal. 20, 1481-1500.

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Ascorbate as a “redox sensor” and protector against irradiation-induced oxidative stress in 32D CL 3 hematopoietic cells and subclones overexpressing human manganese superoxide dismutase

Cited by 35 publications

References 28 publications

Radioprotective gene therapy through retroviral expression of manganese superoxide dismutase

Radioprotective gene therapy through retroviral expression of manganese superoxide dismutase

Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage

Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

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