The relationship between MMPs and pH in whole saliva of radiated head and neck cancer patients.
BACKGROUND
Radiation therapy for head and neck tumour patients may lead to decreased salivary flow, oral mucosal lesions and increased caries experience. Salivary matrix metalloproteinases (MMPs) may participate in the pathogenesis of mucosal lesions and dentinal caries. The aims of this study were: (i) to assay the presence, molecular forms and proteolytic activity of MMP-8 (collagenase-2) and MMP-9 (gelatinase B) in the whole saliva of head and neck cancer patients having radiation therapy; (ii) to see whether salivary pH affects the activity of MMP-8 and MMP-9; and (iii) to find out the possible connection between MMP-8 and MMP-9 with the eruption of oral mucosal lesions during radiation therapy.


METHODS
The whole saliva samples of 39 head and neck cancer patients having radiation therapy were collected before, during and after radiation therapy, and saliva flow rate, pH, buffer capacity, Streptococcus mutans, Lactobacillus and Candida albicans were measured. Any oral mucosal lesions were examined during each visit. The levels of MMP-8 were measured by immunofluorometric assay (IFMA) and the presence of different MMP-8 forms was analysed using Western immunoblotting. The presence and molecular forms of MMP-9 were analyzed by gelatin zymography. MMP-9 capture activity assay was used to determine the APMA-activated MMP-9 activity (total) and the endogenously active MMP-9 (free activity).


RESULTS
Salivary flow rate, buffer capacity and pH decreased, and the levels of Lactobacilli increased significantly, during the first half of the radiation therapy. The endogenously activated salivary MMP-9 correlated with low salivary pH (P = 0.013). No connection was found between the oral mucosal lesions and salivary MMP-8 or MMP-9.


CONCLUSIONS
In this study, salivary MMP-8 or MMP-9 did not correlate with the presence of radiation induced oral mucosal lesions, but the activation of MMP-9 may be dependent on pH.
Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland.
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T
Vuotila
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Ylikontiola
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Sorsa
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H
Luoto
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R
Hanemaaijer
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Salo
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Tjäderhane
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D016009:Chi-Square Distribution; D016371:Cranial Irradiation / Q000009:adverse effects*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005470:Fluorometry; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology / Q000528:radiation effects*; D019226:Oral Ulcer / Q000209:etiology; D012463:Saliva / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology / Q000528:radiation effects*; D012636:Secretory Rate / Q000528:radiation effects; D018709:Statistics, Nonparametric
D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9