Relations between non-protein sulfydryl levels in the nucleus and cytoplasm, tumor oxygenation, and clinical outcome of patients with uterine cervical carcinoma.
OBJECTIVE
The non-protein sulfydryls (NPSH) glutathione and cysteine are able to effect chemical repair of radiation-induced DNA damage, particularly under hypoxic conditions, and are implicated in radioresistance. The levels of NPSH in the nucleus are predicted to be more important than those in cytoplasm. We, therefore, investigated the relation between nuclear NPSH and the clinical outcome of radical radiotherapy (RT).


METHODS
A fluorescence image analysis technique to measure nuclear NPSH was developed, based on the SH-reactive probe 1(4-chloromercuryphenyl-azo-2-naphthol) and the DNA dye 4,6-diamidino-2-phenylindole. This was used to measure nuclear and tissue NPSH levels in biopsies obtained from 58 patients with locally advanced uterine cervical carcinoma, treated with radical RT.


RESULTS
An approximately twofold range in the nuclear and tissue NPSH levels between individual tumors was found, although the intratumoral heterogeneity was much smaller. Nuclear and tissue NPSH values correlated closely in all cases. No statistically significant associations were noted between NPSH levels and tumor size, stage, or tumor hypoxia as determined at the time of biopsy using an Eppendorf po(2) probe. The response to RT and patient survival did not correlate with tumor NPSH.


CONCLUSIONS
These results did not support the existence of an independently regulated nuclear pool of NPSH and showed that tissue and nuclear NPSH are not predictive of the outcome of patients with locally advanced cervical carcinomas treated with RT.
Hedley
David W
DW
Department of Medical Oncology and Hematology, Toronto, ON, Canada. david.hedley@uhn.on.ca
Nicklee
Trudey
T
Moreno-Merlo
Fernando
F
Pintilie
Melania
M
Fyles
Anthony
A
Milosevic
Michael
M
Hill
Richard P
RP
D002467:Cell Nucleus / Q000737:chemistry*; D003545:Cysteine / Q000032:analysis*; D003593:Cytoplasm / Q000737:chemistry*; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage; D005978:Glutathione / Q000032:analysis*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D010663:Phenylmercury Compounds / Q000008:administration & dosage; D002583:Uterine Cervical Neoplasms / Q000737:chemistry*
D005456:Fluorescent Dyes; D007211:Indoles; D010663:Phenylmercury Compounds; C007293:DAPI; D005978:Glutathione; D003545:Cysteine; C031504:mercury orange