Predictive and prognostic significance of glutathione levels and DNA damage in cervix cancer patients undergoing radiotherapy.
OBJECTIVE
To assess the predictive significance of serum glutathione (GSH) and tumor tissue DNA damage in the treatment of cervical cancer patients undergoing chemoradiotherapy.


METHODS
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.
Department of Radiotherapy, Shirdi Saibaba Cancer Hospital, Kasturba Medical College, Manipal, Karnataka, India.
Mamidipudi Srinivasa
MS
Vidyasagar
Maheedhar
M
Kodali
Pu
P
Prakash Saxena
Dinesh
D
Upadhya
Chilakapati
C
Murali Krishna
Bejadi Manjunath
BM
Vadhiraja
Donald Jerard
DJ
Fernandes
Satish Rao
SR
Bola Sadashiva
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000097:blood; D001918:Brachytherapy / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy / Q000379:methods; D004249:DNA Damage; D019583:Dose Fractionation, Radiation; D005260:Female; D005978:Glutathione / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005978:Glutathione; D002945:Cisplatin