Radiotherapy for head and neck malignancies is associated with increased salivary platelet-activating factor content

Purpose/Objective: Oral mucositis, characterized by pronounced erythema, edema, atrophy, and ulceration, remains a common complication of radiotherapeutic treatment of head and neck malignancies. These radiation-induced morbidities can cause a temporary cessation or indeed reduction in the extent of radiotherapy dose employed, compromising the likelihood of tumor cure. The precise pathogenic mechanisms involved in the development of radiation mucositis remain ill-defined. Platelet-activating factor (PAF), a pivotal mediator of acute inflammatory reactions, has been implicated in radiation-induced mucositis (McManus et al Lab Invest 68:118-124 1993). However, these data are limited in terms both of patient numbers, and time-course. The present study evaluated saliva PAF levels in patients receiving radiotherapy for head and neck malignancies in terms of levels prior to, during, and after the completion of radiotherapy. Materials and Methods: Saliva samples (1-2 mL) were obtained from 14 patients with oral cancer, and from 14 control non-malignant individuals. Saliva samples from the oral cancer patients were collected prior to the initiation of treatment, after the administration of 30 Gy, and at the completion of the course of radiotherapy. PAF was extracted from the saliva samples using a chloroform methanol mixture (2:1). Further purification was accomplished by washing the extracts through silica minicolumns. Measurements of PAF content were performed using a scintillation proximity assay system (Amersham, UK). This combined the use of a high specific activity 3H-PAF with an antibody specific for PAF. Results: The PAF content of saliva obtained from patients prior to the initiation of radiotherapy was 226 ± 55 ng/mL, (mean ± SE). This was significantly greater than the value of 25 ± 11 ng/mL (p value = 0.003; 2-tail t test) measured in the saliva from the control individuals. Irradiation was associated with a significant increase in the PAF content of saliva. Thus, after a dose of 30 Gy, at which time all patients exhibited oral mucositis, salivary PAF levels increased to a mean value of 501 ± 104 ng/mL (p = 0.002). By the completion of radiotherapy, the mucositis had resolved in some, but not all, of the patients; mean saliva PAF content had declined to a value of 321 ± 51 ng/mL, but remained significantly elevated compared with the pre-treatment value (p = 0.003). Conclusion: The development of mucositis in patients receiving radiotherapy for the treatment of oral cancers is associated with a significant increase in the PAF content of saliva. These results support the hypothesis that PAF may play a pathogenic role in the evolution of radiation-induced mucositis. Attenuation of this increase in PAF might lead to a reduction in the severity of this radiation-induced morbidity