Influence of plasma glutathione levels on radiation mucositis.
OBJECTIVE
To test the hypothesis that there is a link between plasma glutathione (GSH) or other antioxidants (uric acid, ascorbate) and the severity of radiation mucositis following radiation treatment of tumors of the head and neck.


METHODS
Patients with carcinomas of the head-and-neck region were treated with the continuous hyperfractionated accelerated radiotherapy (CHART) regimen (54 Gy in 36 fractions over 12 days). Samples of blood plasma were analyzed for GSH, cysteine, urate, and ascorbate by high-pressure liquid chromatography. Patients were graded for dysphagia and requirement for analgesics. The areas under the curves of scores over 2-6 weeks following treatment were computed, and Spearman's rank-correlation coefficient was used to test for an association between plasma GSH levels (or those of other antioxidants) and mucositis.


RESULTS
The pretreatment plasma GSH level in 18 patients scored in the study was 1.0 +/- 0.7 M. Analysis of these and the dysphagia scores produced a correlation coefficient of 0.22 (confidence interval -0.28, 0.61; p = 0.39). No correlation was seen between mucositis severity and other measures of plasma antioxidants: cysteine (7.6 +/- 1.7 M), cysteine + GSH (8.6 +/- 1.9 M), uric acid (317 +/- 86 M), ascorbate (29 +/- 20 M), or whole-blood GSH concentrations (1,010 +/- 239 M).


CONCLUSIONS
The measurements of approximately micromolar levels of plasma GSH, or about 10 M cysteine + GSH (almost all of the total nonprotein thiols), are consistent with most other published data for either healthy adults or cancer patients; however, the values reported in an earlier study, suggesting a link between GSH and mucositis, are much higher. The hypothesis of a possible link between radiation mucositis and plasma-free (nonprotein) thiols was not supported.
Wardman
P
P
Gray Cancer Institute, Mount Vernon Hospital, Northwood, Middlesex, UK. wardman@gci.ac.uk
Folkes
L K
LK
Bentzen
S M
SM
Stratford
M R
MR
Hoskin
P J
PJ
Phillips
H
H
Jackson
S
S
D001205:Ascorbic Acid / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D003545:Cysteine / Q000097:blood; D019583:Dose Fractionation, Radiation; D005978:Glutathione / Q000097:blood*; D006801:Humans; D016014:Linear Models; D009061:Mouth Mucosa / Q000528:radiation effects*; D009062:Mouth Neoplasms / Q000532:radiotherapy*; D012680:Sensitivity and Specificity; D013280:Stomatitis / Q000097:blood* / Q000209:etiology; D014527:Uric Acid / Q000097:blood
D014527:Uric Acid; D005978:Glutathione; D003545:Cysteine; D001205:Ascorbic Acid