Predictive and prognostic significance of glutathione levels and DNA damage in cervix cancer patients undergoing radiotherapy

Mamidipudi Srinivasa Vidyasagar, Maheedhar Kodali, Pu Prakash Saxena, Dinesh Upadhya, Chilakapati Murali Krishna, Bejadi Manjunath Vadhiraja, Donald Jerard Fernandes, Satish Rao Bola Sadashiva

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Abstract

Purpose: To assess the predictive significance of serum glutathione (GSH) and tumor tissue DNA damage in the treatment of cervical cancer patients undergoing chemoradiotherapy. Methods and Materials: This study included subjects undergoing hysterectomy (for normal cervix tissue) and cervical cancer patients who underwent conventional concurrent chemoradiotherapy (cisplatin once per week for 5 weeks with concurrent external radiotherapy of 2 Gy per fraction for 5 weeks, followed by two applications of intracavitary brachytherapy once per week after 2 weeks' rest). Blood was collected after two fractions, whereas both blood and tissues were collected after five fractions of radiotherapy in separate groups of subjects. Serum for total GSH content and tissues were processed for single-cell gel electrophoresis (SCGE) assay for DNA damage analysis. Clinical tumor radioresponse was assessed 2 months after the completion of treatment as complete responders (CR) (100% shrinkage), partial responders (PR) (>50%), and nonresponders (NR) (<50%). Results: Serum GSH content depleted significantly after a total dose of 4 Gy and 10 Gy of radiotherapy with a single dose of cisplatin, which was significantly lesser in NR than of CR patients. Similarly, Olive Tail Moment, the index of DNA damage, indicated significantly higher values in the fifth fraction of radiotherapy (5-RT) than in pretreatment. The DNA damage after 5-RT in the NR subgroup was significantly lower than that of CR. Conclusions: Serum GSH analysis and tumor tissue SCGE assay found to be useful parameters for predicting chemoradioresponse prior to and also at an early stage of treatment of cervical cancers.

Original languageEnglish
Pages (from-to)343-349
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume78
Issue number2
DOIs
Publication statusPublished - 01-10-2010

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glutathione
transponders
Uterine Cervical Neoplasms
DNA Damage
Glutathione
radiation therapy
Radiotherapy
deoxyribonucleic acid
cancer
serums
damage
Comet Assay
tumors
Chemoradiotherapy
electrophoresis
Serum
Cisplatin
blood
gels
dosage

All Science Journal Classification (ASJC) codes

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

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title = "Predictive and prognostic significance of glutathione levels and DNA damage in cervix cancer patients undergoing radiotherapy",
abstract = "Purpose: To assess the predictive significance of serum glutathione (GSH) and tumor tissue DNA damage in the treatment of cervical cancer patients undergoing chemoradiotherapy. Methods and Materials: This study included subjects undergoing hysterectomy (for normal cervix tissue) and cervical cancer patients who underwent conventional concurrent chemoradiotherapy (cisplatin once per week for 5 weeks with concurrent external radiotherapy of 2 Gy per fraction for 5 weeks, followed by two applications of intracavitary brachytherapy once per week after 2 weeks' rest). Blood was collected after two fractions, whereas both blood and tissues were collected after five fractions of radiotherapy in separate groups of subjects. Serum for total GSH content and tissues were processed for single-cell gel electrophoresis (SCGE) assay for DNA damage analysis. Clinical tumor radioresponse was assessed 2 months after the completion of treatment as complete responders (CR) (100{\%} shrinkage), partial responders (PR) (>50{\%}), and nonresponders (NR) (<50{\%}). Results: Serum GSH content depleted significantly after a total dose of 4 Gy and 10 Gy of radiotherapy with a single dose of cisplatin, which was significantly lesser in NR than of CR patients. Similarly, Olive Tail Moment, the index of DNA damage, indicated significantly higher values in the fifth fraction of radiotherapy (5-RT) than in pretreatment. The DNA damage after 5-RT in the NR subgroup was significantly lower than that of CR. Conclusions: Serum GSH analysis and tumor tissue SCGE assay found to be useful parameters for predicting chemoradioresponse prior to and also at an early stage of treatment of cervical cancers.",
author = "Vidyasagar, {Mamidipudi Srinivasa} and Maheedhar Kodali and {Prakash Saxena}, Pu and Dinesh Upadhya and {Murali Krishna}, Chilakapati and Vadhiraja, {Bejadi Manjunath} and Fernandes, {Donald Jerard} and {Bola Sadashiva}, {Satish Rao}",
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Predictive and prognostic significance of glutathione levels and DNA damage in cervix cancer patients undergoing radiotherapy. / Vidyasagar, Mamidipudi Srinivasa; Kodali, Maheedhar; Prakash Saxena, Pu; Upadhya, Dinesh; Murali Krishna, Chilakapati; Vadhiraja, Bejadi Manjunath; Fernandes, Donald Jerard; Bola Sadashiva, Satish Rao.

In: International Journal of Radiation Oncology Biology Physics, Vol. 78, No. 2, 01.10.2010, p. 343-349.

Research output: Contribution to journalArticle

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AU - Vidyasagar, Mamidipudi Srinivasa

AU - Kodali, Maheedhar

AU - Prakash Saxena, Pu

AU - Upadhya, Dinesh

AU - Murali Krishna, Chilakapati

AU - Vadhiraja, Bejadi Manjunath

AU - Fernandes, Donald Jerard

AU - Bola Sadashiva, Satish Rao

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N2 - Purpose: To assess the predictive significance of serum glutathione (GSH) and tumor tissue DNA damage in the treatment of cervical cancer patients undergoing chemoradiotherapy. Methods and Materials: This study included subjects undergoing hysterectomy (for normal cervix tissue) and cervical cancer patients who underwent conventional concurrent chemoradiotherapy (cisplatin once per week for 5 weeks with concurrent external radiotherapy of 2 Gy per fraction for 5 weeks, followed by two applications of intracavitary brachytherapy once per week after 2 weeks' rest). Blood was collected after two fractions, whereas both blood and tissues were collected after five fractions of radiotherapy in separate groups of subjects. Serum for total GSH content and tissues were processed for single-cell gel electrophoresis (SCGE) assay for DNA damage analysis. Clinical tumor radioresponse was assessed 2 months after the completion of treatment as complete responders (CR) (100% shrinkage), partial responders (PR) (>50%), and nonresponders (NR) (<50%). Results: Serum GSH content depleted significantly after a total dose of 4 Gy and 10 Gy of radiotherapy with a single dose of cisplatin, which was significantly lesser in NR than of CR patients. Similarly, Olive Tail Moment, the index of DNA damage, indicated significantly higher values in the fifth fraction of radiotherapy (5-RT) than in pretreatment. The DNA damage after 5-RT in the NR subgroup was significantly lower than that of CR. Conclusions: Serum GSH analysis and tumor tissue SCGE assay found to be useful parameters for predicting chemoradioresponse prior to and also at an early stage of treatment of cervical cancers.

AB - Purpose: To assess the predictive significance of serum glutathione (GSH) and tumor tissue DNA damage in the treatment of cervical cancer patients undergoing chemoradiotherapy. Methods and Materials: This study included subjects undergoing hysterectomy (for normal cervix tissue) and cervical cancer patients who underwent conventional concurrent chemoradiotherapy (cisplatin once per week for 5 weeks with concurrent external radiotherapy of 2 Gy per fraction for 5 weeks, followed by two applications of intracavitary brachytherapy once per week after 2 weeks' rest). Blood was collected after two fractions, whereas both blood and tissues were collected after five fractions of radiotherapy in separate groups of subjects. Serum for total GSH content and tissues were processed for single-cell gel electrophoresis (SCGE) assay for DNA damage analysis. Clinical tumor radioresponse was assessed 2 months after the completion of treatment as complete responders (CR) (100% shrinkage), partial responders (PR) (>50%), and nonresponders (NR) (<50%). Results: Serum GSH content depleted significantly after a total dose of 4 Gy and 10 Gy of radiotherapy with a single dose of cisplatin, which was significantly lesser in NR than of CR patients. Similarly, Olive Tail Moment, the index of DNA damage, indicated significantly higher values in the fifth fraction of radiotherapy (5-RT) than in pretreatment. The DNA damage after 5-RT in the NR subgroup was significantly lower than that of CR. Conclusions: Serum GSH analysis and tumor tissue SCGE assay found to be useful parameters for predicting chemoradioresponse prior to and also at an early stage of treatment of cervical cancers.

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