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Radiation induced oxidative stress: I. Studies in Ehrlich solid tumor in mice
A Agrawal1, D Choudhary, M Upreti
1School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Molecular and Cellular Biochemistry
|October 30, 2001
Summary
Irradiated tumors show increased antioxidant enzymes, potentially reducing radiation therapy effectiveness. This enhanced antioxidant status in cancer may limit therapeutic gains and worsen patient outcomes.
Area of Science:
- Oncology
- Radiation Biology
- Biochemistry
Background:
- Tumor response to ionizing radiation is crucial for improving cancer treatment and reducing patient morbidity.
- Antioxidant status is a key factor influencing a tumor's response to radiation therapy (radioresponse).
Purpose of the Study:
- To investigate the modulation of antioxidant status in tumors following gamma irradiation.
- To examine the relationship between antioxidant enzyme activity and radiation-induced oxidative stress in Ehrlich solid tumors.
Main Methods:
- Swiss albino male mice bearing Ehrlich solid tumors were exposed to varying doses of gamma rays (0-9 Gy).
- Enzymes involved in antioxidant functions (SOD, GST, DTD, GSH) were quantified in tumor tissues.
- Oxidative damage markers, lactate dehydrogenase (LDH) activity, nitric oxide levels, and DNA fragmentation were assessed.
- Western Blot analysis was used to confirm protein expression changes for GST.
Main Results:
- Specific activity of superoxide dismutase (SOD) increased with radiation dose, declining after 6 Gy.
- Glutathione S-transferase (GST), dihydrolipoamide dehydrogenase (DTD), and glutathione (GSH) showed progressive increases with dose.
- Western Blot confirmed increased GST protein expression, supporting enhanced enzyme activity.
- Radiation exposure led to increased peroxidative damage, DNA fragmentation, LDH activity, and nitric oxide levels.
Conclusions:
- Elevated antioxidant status in irradiated tumors, evidenced by increased SOD, GST, DTD, and GSH, may counteract radiation effects.
- These adaptive antioxidant responses are linked to radiation-induced oxidative stress.
- The enhanced antioxidant capacity of tumors could limit the effectiveness of radiation therapy, potentially reducing therapeutic gain and adversely impacting patient outcomes.