Sporadic versus syndromic keratocysts-Can we predict treatment outcome? A review of 102 cysts.

OBJECTIVES: Keratocystic odontogenic tumor (KCOT) demonstrates variable growth mechanisms and biologic behavior, partly due to origin and histology. We looked for the most contributing factors in predicting outcome of treatment. SUBJECTS AND METHODS: We retrospectively reviewed 118 medical files of patients diagnosed with KCOT (by tissue biopsy before surgical treatment) with/without nevoid basal cell carcinoma syndrome (NBCCS) from 1995 to 2015. Data were recorded and analyzed statistically to determine the treatment-outcome correlation. KCOTs in NBCCS patients were termed "syndromic" and random KCOTs termed "sporadic." RESULTS: Of 102 cysts, 32 were diagnosed with NBCCS. Sporadic KCOTs were significantly larger upon diagnosis (p < .017). Factors most indicative of postsurgical complications are older age (p < .011), upper jaw location, and size of lesion ≥9.5 cm². Sporadic KCOTs significantly increased the chances of complications approximately threefold (p < .043). Higher recurrence rate was significant in syndromic cysts (47%) compared to sporadic cysts (20%) (p < .009). Recurrence time was 3 years on average. CONCLUSIONS: Postsurgical complications may be expected in: older patients, upper jaw location, extensive lesions, and sporadic KCOT. Most KCOT recurrence is diagnosed 3 years from treatment.

Pleural fluid analysis of lung cancer vs benign inflammatory disease patients.

BACKGROUND: Correct diagnosis of pleural effusion (PE) as either benign or malignant is crucial, although conventional cytological evaluation is of limited diagnostic accuracy, with relatively low sensitivity rates. METHODS: We identified biological markers accurately detected in a simple PE examination. We analysed data from 19 patients diagnosed with lung cancer (nine adeno-Ca, five non-small-cell Ca (not specified), four squamous-cell Ca, one large-cell Ca) and 22 patients with benign inflammatory pathologies: secondary to trauma, pneumonia or TB. RESULTS: Pleural effusion concentrations of seven analysed biological markers were significantly lower in lung cancer patients than in benign inflammatory patients, especially in matrix metalloproteinase (MMP)-9, MMP-3 and CycD1 (lower by 65% (P<0.000003), 40% (P<0.0007) and 34% (P<0.0001), respectively), and in Ki67, ImAnOx, carbonyls and p27. High rates of sensitivity and specificity values were found for MMP-9, MMP-3 and CycD1: 80 and 100%; 87 and 73%; and 87 and 82%, respectively. CONCLUSION: Although our results are of significant merit in both the clinical and pathogenetic aspects of lung cancer, further research aimed at defining the best combination for marker analysis is warranted. The relative simplicity in analysing these markers in any routine hospital laboratory may result in its acceptance as a new diagnostic tool.

Salivary profile and oxidative stress in children and adolescents with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterized by altered exocrine secretions; however, no comprehensive compositional profile of CF serous and mucous saliva secretions has been published. DESIGN: We analyzed salivary flow rate and composition, and oxidative stress-related parameters, comparing CF patients with non-CF bronchiectasis patients and the healthy controls. RESULTS: Median salivary magnesium concentration and lactate dehydrogenase activity were significantly lower in CF patients than in the healthy controls. Salivary total protein concentration was 45% higher in CF patients than in non-CF bronchiectasis patients. CF patients showed 8% lower levels of peroxidase compared with non-CF bronchiectasis. Salivary total antioxidant status, superoxide dismutase and uric acid values in the CF group were higher by 15%, 35% and 31%, respectively, than in both control groups. CONCLUSIONS: Cystic fibrosis patients demonstrated altered salivary profile, especially in antioxidant enzymatic and molecular activity, possibly resulting from the oral cavity's ongoing inflammatory and oxidative process. Free radical mechanisms may be involved in CF pathogenesis.

Salivary analysis of oral cancer biomarkers.

BACKGROUND: Oral cancer is a common and lethal malignancy. Direct contact between saliva and the oral cancer lesion makes measurement of tumour markers in saliva an attractive alternative to serum testing. METHODS: We tested 19 tongue cancer patients, measuring the levels of 8 salivary markers related to oxidative stress, DNA repair, carcinogenesis, metastasis and cellular proliferation and death. RESULTS: Five markers increased in cancer patients by 39-246%: carbonyls, lactate dehydrogenase, metalloproteinase-9 (MMP-9), Ki67 and Cyclin D1 (CycD1) (P< or =0.01). Three markers decreased by 16-29%: 8-oxoguanine DNA glycosylase, phosphorylated-Src and mammary serine protease inhibitor (Maspin) (P< or =0.01). Increase in salivary carbonyls was profound (by 246%, P=0.012); alterations in CycD1 (87% increase, P=0.000006) and Maspin (29% decrease, P=0.007) were especially significant. Sensitivity values of these eight analysed markers ranged from 58% to 100%; specificity values ranged from 42% to 100%. Both values were especially high for the CycD1 and Maspin markers, 100% for each value of each marker. These were also high for carbonyls, 90% and 80%, respectively, and for MMP-9, 100% and 79%, respectively. CONCLUSION: The significance of each salivary alteration is discussed. As all alterations correlated with each other, they may belong to a single carcinogenetic network. Cancer-related changes in salivary tumour markers may be used as a diagnostic tool for diagnosis, prognosis and post-operative monitoring.

Salivary and gustatory alterations among bulimia nervosa patients.

OBJECTIVE AND DESIGN: This study systematically examined salivary composition and taste perception and monitored related subjective complaints in a group of bulimia nervosa (BN) patients. SUBJECTS: Fifty-two consenting female individuals participated in the current cross-sectional study, 26 patients diagnosed with BN according to the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria (mean age: 24+/-7 years) and 26 healthy controls matching in age and body mass index (BMI). METHODS: All participants were given diagnostic BN-related questionnaires, had taste and salivary-composition analyses and were monitored for oral sensorial complaints. The patients were also subjected to psychological and psychiatric examinations focusing on established criteria known to be pathognomonic of the disease (including binge eating episodes, depression, impulsive traits, enhanced awareness of body image, typical compensatory behavior, and so on). RESULTS: The self-answered questionnaires of Bulimic Investigatory Test Edinburgh (BITE), Beck Depression Inventory (BDI), brief symptom inventory (BSI) and impulsivity scale (IS) revealed highly significant differences between the two groups with respect to the various BN diagnostic symptoms of the patients (P=0.0001). Subjective and objective examinations showed an overall disturbed salivary and taste profile in BN patients, who complained of xerostomia (dry mouth) and taste aberration or oral burning sensation. CONCLUSIONS: Regardless of the specific mechanism responsible for the disturbed salivary and taste profile in BN patients, these observed changes are associated with active illness. Accordingly, administration of therapeutic agents, including antioxidants, anti-inflammatory drugs and saliva substitutes, to the oral cavity (and maybe even systemically) of BN patients should be considered.

Maxillary tumour-induced osteomalacia.

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic form of renal phosphate wasting that results in severe hypophosphatemia, defective vitamin D metabolism, and osteomalacia. In the case reported here, maxillary TIO was not diagnosed for 6years, although initial complaints were reported when the patient was 12years old. Meanwhile she suffered from profound growth limitation, pain, weakness, and spontaneous multiple bone fractures, culminating in complete loss of ambulatory ability and severe limitation in daily activities. At age 18years, she finally received an accurate diagnosis and definitive treatment was administered. She underwent a partial maxillectomy with complete removal of the tumour, resulting in a full cure. Shortly afterwards the patient regained the ability to walk, no longer needing the wheelchair to which she had been confined. This definitive diagnosis was based on three modalities: (1) fibroblast growth factor 23 analysis (high levels of the secreted hormone were found on the left side of the maxilla in the facial vein and pterygoid plexus, pinpointing the tumour location), (2) octreotide scan, and (3) 68Ga-DOTA-NOC-PET/CT. TIO removal via partial maxillectomy led to a complete reversal of this patient's health condition, restoring her ability to walk and function. The importance of prompt employment of these diagnostic modalities and the high level of clinical suspicion required in such cases are clear.

Age- and flow-dependency of salivary viscoelasticity.

Measuring salivary viscoelasticity (by relaxation times) is of paramount importance, since salivary rheology behavior has been associated with the development of oral disease conditions (such as dental caries) in animal and human model studies. In addition, novel and improved methods to evaluate salivary distribution and lubrication are of clinical interest. We used a novel method for measuring the viscoelasticity of saliva secreted from the different glands, at rest or under stimulation and at different ages, all conditions where different viscoelastic properties might be clinically important. Submandibular/sublingual salivary viscoelasticity was significantly higher than that of parotid saliva, especially under stimulation. In addition, an age-related reduction in flow rate (by 62%) was demonstrated, accompanied by an increase in both relaxation time (by 54%) and protein (by 48%). Increased salivary viscoelasticity results in compromised salivary rheology and lubrication properties, which may render the oral cavities of the elderly and other xerostomic persons more vulnerable.

Altered salivary profile in heavy smokers and its possible connection to oral cancer.

Saliva is the first biological fluid to encounter inhaled cigarette smoke, whose numerous carcinogens and oxidants are responsible for the oral cancer so prevalent among smokers. Whole saliva, collected from 25 consenting heavy smokers and from a control group of 25 age- and gender-matched non-smokers, was subjected to sialochemical, biochemical, immunological and oxidative analyses. The mean flow rate was significantly higher in smokers than in non-smokers, as were the median activity value of superoxide dismutase (SOD) and the total salivary antioxidant capacity (ImAnOx) (by 32% and 12%, respectively, p=0.05). The salivary carbonyl concentration (an oxidative stress indicator) was significantly higher by 126% (p=0.0006) among smokers, while lactate dehydrogenase, albumin, total immunoglobulin G, and the metalloproteinases MMP-2 and MMP-9 concentrations were significantly lower in the smokers, by 86% (p=0.003), 65% (p=0.003), 61% (p=0.048), 35% (p=0.005) and 55% (p=0.035), respectively. Apparently, the oral cavity''s salivary antioxidant system fails to cope with the severe attack of reactive oxygen species originating in cigarette smoke. Moreover, various other salivary functional and protective parameters also decreased among the smokers. Hence, further research aimed at examining the possibility of administration of agents as antioxidants or saliva substitutes to the oral cavity of smokers should be considered.

Cigarette smoke-induced reduction in binding of the salivary translocator protein is not mediated by free radicals.

Oral cancer is the most common malignancy of the head and neck and its main inducer is exposure to cigarette smoke (CS) in the presence of saliva. It is commonly accepted that CS contributes to the pathogenesis of oral cancer via reactive free radicals and volatile aldehydes. The 18 kDa translocator protein (TSPO) is an intracellular receptor involved in proliferation and apoptosis, and has been linked to various types of cancer. The presence of TSPO in human saliva has been linked to oral cancer, and its binding affinity to its ligand is reduced following exposure to CS. In the present study we wished to further investigate the mechanism behind the CS-induced reduction of TSPO binding by exploring the possible mediatory role of reactive oxygen species (ROS) and volatile aldehydes in this process. We first analyzed TSPO binding in control saliva and in saliva exposed to CS in the presence and absence of various antioxidants. These experiments found that TSPO binding ability was not reversed by any of the antioxidants added, suggesting that CS exerts its effect on TSPO via mechanisms that do not involve volatile aldehydes and free radicals tested. Next, we analyzed TSPO binding in saliva following addition of exogenous ROS in the form of H2O2. These experiments found that TSPO binding was enhanced due to the treatment, once again showing that the CS-induced TSPO binding reduction is not mediated by this common form of ROS. However, the previously reported CS-induced reduction in salivary TSPO binding together with the role of TSPO in cells and its link to cancer strongly suggest that TSPO has a critical role in the pathogenesis of CS-induced oral cancer. The importance of further elucidating the mechanisms behind it should be emphasized.

Extended-term effects of head and neck irradiation in a rodent.

Radiotherapy to the head and neck is a common treatment for malignancies of the region. Unfortunately, exposure to irradiation often results in a variety of complications, most of which are localised and expressed in the short term following irradiation. However, prolonged and systemic effects may have greater clinical importance as the survival rate of head and neck irradiated patients is increasing yearly. Six groups of 18-20 rats were evaluated during a 1 year study. The non-irradiated control group was compared with 2.5 Gy, 5, 7.5, 10 and 15 Gy irradiated groups. We found a dose-dependent reduction in both survival and body weight in our rat models following a delayed, prolonged and chronic process. Dying animals were emaciated, dehydrated and starved, and many were blind and immunocompromised. While the exact underlying mechanism of this delayed, but devastating, phenomenon has not yet been determined, the delayed xerostomia inflicted on these animals may, at least partially, explain it. The clinical implications for head and neck patients require further evaluation, but our data should be considered, in the context of the available evidence for the long-term effects of head and neck irradiation in humans.

Protection against irradiation-induced damage to salivary glands by adrenergic agonist administration.

PURPOSE: Irradiation [IR]-induced damage to major salivary glands is an entity first described at the beginning of our century, yet its underlying mechanism is still enigmatic. Exposure of the salivary glands to IR is often inevitable when delivering radiotherapy for malignancies of the head and neck region. Frequently, this results in rapidly developing, life-long severe xerostomia for which no adequate prevention or treatment is available. The purpose of this study was to examine the role of secretion granules in serous cells of the parotid (P) and submandibular (SM) glands as mediators in the IR-induced salivary damage. Functional parameters (flow rate and gland weight), and total body weight were examined at both early term (4 days) and extended term (2 months) post-IR in male Wistar rats exposed to 15 Gy of head and neck irradiation following stimulation for granule secretion (degranulation). METHODS AND MATERIALS: At 4 days, it was demonstrated that IR reduced P flow rate, P gland weight, total body weight, and submandibular/sublingual gland weight by 89, 33, 30, and 32% (p < 0.01), respectively, while SM flow rate was not altered significantly. At 2 months, these parameters were reduced by 59, 37, 31, and 37%, respectively, and the SM flow rate was reduced by 39% (p < 0.01). RESULTS: Pilocarpine, a muscarinsic agonist which, albeit its efficacy as a salivary watery secretion stimulator, causes only limited degranulation, did not protect significantly any of the reduced parameters at either term. In contrast, cyclocytidine, an adrenergic agonist that is a very potent salivary degranulating agent, protected the P against the weight loss at 4 days and 2 months, and against the flow rate reduction at 2 months. The P weight and flow rate were protected to the extent that their values were not significantly different than those of the nonirradiated controls. Cyclocytidine also partially protected against the body weight reduction at 2 months. Our results emphasize the importance of secretion granules as mediatory agents in IR-induced P damage, and more so at the extended term. The demonstrated protective role of adrenergic agonists against IR damage to the P may be of importance in the clinical setting.

Sjögren's syndrome induced by estrogen therapy.

OBJECTIVE: To describe a possible role for estrogen in the induction or acceleration of Sjögren's syndrome (SS). METHOD: Two healthy young women who received estrogen-increasing therapy and then developed full-blown SS are described. The relationship between SS and estrogen therapy is discussed and the available literature reviewed. RESULTS: Both women developed SS 3 years after starting estrogen-increasing treatment. The syndrome was severe in the first patient, who was treated with a high dosage of estrogen; the disease was moderate in the second patient, who received a lower estrogen dosage. CONCLUSION: Estrogen may play a role in the pathogenesis of SS in some patients.

Pilocarpine hydrochloride relieves xerostomia in chronic graft-versus-host disease: a sialometrical study.

Bone marrow transplantation is considered to be the treatment of choice for various hematological and solid malignancies, as well as for bone marrow failure syndromes and some genetic diseases. Unfortunately, a great number of patients who receive allogeneic BMT suffer from graft-versus-host disease (GVHD) following the procedure. Xerostomia is considered to be one of the most annoying complications of chronic GVHD (cGVHD), and the rapidly growing number of BMT patients with prolonged survival renders GVHD-related xerostomia a major clinical problem. As pilocarpine hydrochloride has been shown to relieve xerostomia in other disease categories, we administered pilocarpine hydrochloride 30 mg/day to six cGVHD patients and measured their whole saliva, parotid and submandibular-sublingual flow rates in both resting and stimulated conditions. Mean values of flow rates of whole saliva in resting conditions at 2 weeks, 2 months and 6 months following administration of pilocarpine hydrochloride 30 mg/day were 0.71 +/- 0.12 ml/min, 0.59 +/- 0.07 ml/min and 0.56 +/- 0.11 ml/min, respectively. In stimulated conditions, mean values were 1.7 +/- 0.3 ml/min, 1.0 +/- 0.17 ml/min and 0.94 +/- 0.21 ml/min, respectively. The mean values of whole saliva flow rates under both conditions represented an increase of 224-284% and 134-247%, respectively (P < 0.01). The pattern and magnitude of parotid and submandibular-sublingual flow rate increases following pilocarpine hydrochloride administration were similar. Patients were followed for 6 months and demonstrated increased levels of secretion, with some reduction after the initial peak values. The medication was discontinued at 2 months and reinstated after 2 weeks in three patients. This resulted in rapid flow rate reduction followed by another profound increase. Contrary to the sialometrical analysis, the subjective scoring showed no fluctuations during the study period. We discuss these results in the context of the clinical experience of xerostomic patients in whom even a minute increase in secretion may be significant. Our results demonstrate that objective and subjective relief from xerostomia in cGVHD patients can be achieved with the routine oral administration of pilocarpine hydrochloride.

Major salivary gland dysfunction in patients with hematological malignancies receiving interleukin-2-based immunotherapy post-autologous blood stem cell transplantation (ABSCT).

lnterleukin-2 (IL-2) is known to cause xerostomia and skin manifestations similar to graft-versus-host disease (GVHD). We therefore evaluated major salivary gland function in patients with hematological malignancies treated with IL-2 and interferon-alpha (IFN-alpha) after ABSCT. Eleven patients (seven male, four female) of median age 40 (24-47) were evaluated, seven with non-Hodgkin lymphoma (NHL); one with Hodgkin's disease (HD) and three with acute myelogenous leukemia (AML). Parotid and submandibular salivary gland function was assessed before, during and after IL-2/IFN-alpha administration by evaluation of the salivary flow rate and the composition of secreted saliva. Significant reductions in both the resting and stimulated parotid and submandibular salivary flow rates were observed during IL-2/IFN-alpha immunotherapy compared with the pre- and post-therapy values (P < 0.01), while no hyposalivation was observed in the control patients who underwent ABSCT and did not received IL-2. Sialochemical evaluation revealed a significant increase in potassium concentration (24.4+/-0.6 mEq/l to 28.9+/-1.4 mEq/l) and a significant decrease in sodium concentration (6.7+/-2.1 mEq/l to 3.3+/-1.0 mEq/l) (P < 0.05) in the stimulated parotid gland saliva secreted during IL-2/IFN-alpha administration. Salivary protein concentrations were not altered by the IL-2/IFN-alpha immunotherapy. Similar changes were previously observed in mice and humans with chronic GVHD. We conclude that IL-2 immunotherapy induces major salivary gland dysfunction in humans, similar to our previous observations in patients with chronic GVHD, which may indicate similar pathophysiologic mechanisms.

Mucosal melanoma following autologous stem cell transplantation for non-Hodgkin's lymphoma (NHL).

The incidence of secondary malignancy following autologous stem cell transplantation (ASCT) is increasing. We describe a patient with stage IVB Hodgkin's disease who developed primary amelanotic malignant melanoma of the tongue 18 months following autologous stem cell transplantation. She was treated by partial glossectomy and supra-omohyoid neck dissection followed by cytokine-mediated immunotherapy. Malignant melanoma of the skin is a frequent secondary solid tumor seen in patients undergoing stem cell transplantation. However, mucosal melanoma which is rare by itself (0.2-8%) has never been reported in NHL patients following ASCT. Early diagnosis and initiation of combined local and systemic treatments including immuno-therapy may improve the outcome of this rare but lethal complication.

Major salivary gland dysfunction in human acute and chronic graft-versus-host disease (GVHD).

Salivary gland dysfunction is frequently observed in patients suffering from acute (a) and chronic (c) GVHD. We studied the influence of GVHD on the function of major salivary glands in 20 patients with GVHD (cGVHD, 15; aGVHD, 5). A subjective evaluation of salivary function was performed, in which the score ranged from 0-4 where a higher score indicated more oral dryness. Patients with aGVHD scored 4.0 while patients with cGVHD scored 2.1 (P < 0.01). In addition to this subjective evaluation, patient's salivary flow rates were measured and a reduction of 90% and 60% in aGVHD and cGVHD patients respectively, was observed as compared to controls (P < 0.01; P < 0.05). No hyposalivation was observed in patients who underwent bone marrow transplantation but did not develop GVHD as compared to normal individuals. A direct correlation was observed between the degree of hyposalivation and the severity of the GVHD. Hyposalivation was also documented by scintigraphy of the major salivary glands in the GVHD patients. Furthermore, hyposalivation was associated with extensive mucosal atrophy, erythema, tongue surface depapillation, lichenoid lesions of the buccal and labial mucosa as well as lupus-like lesions. Routine assessment of these glands in patients with GVHD could play a role in monitoring response to therapy.

Novel protection strategy against X-ray-induced damage to salivary glands.

Exposure of the major salivary glands to ionizing radiation often results in severe alterations in structure and function. The mechanism of these effects is still unknown, and no adequate prevention or treatment is yet available. The purpose of this study was to examine a mechanism based on the assumption that redox-active metal ions, which propagate the production of highly reactive free radicals, are responsible for the unique radiosensitivity of salivary glands. Zinc-desferrioxamine (Zn-DFO) was recently reported to be a very potent protector against the injuries induced by such metal ions in the vicinity of sensitive cellular targets. We chose to examine its protective potential against the damage to salivary glands induced by X rays. Head and neck irradiation (15 Gy) was delivered to rats 90 min after the intraperitoneal administration of 20 mg/kg Zn-DFO. This group was compared to two control groups, irradiated and nonirradiated. At 2 months after irradiation, both systemic and salivary parameters were analyzed. The results demonstrated that X irradiation induced a profound attenuation of body weight (30%) and a reduction of parotid gland saliva flow rate (74%), parotid gland weight (36%), submandibular gland/sublingual gland saliva flow rate (46%), and submandibular/sublingual gland weight (24%) (P < 0.01 for all parameters). The content of potassium in parotid gland saliva was increased by 46% (P < 0.01), while the protein content was unaltered. The increase in the potassium concentration of the saliva is considered to be another indication of salivary gland hypofunction. Administration of Zn-DFO prior to irradiation resulted in partial protection against radiation-induced injury to the parotid gland but not the submandibular gland. In the Zn-DFO-treated and irradiated group, the parotid gland saliva flow rate was reduced by 42%, the weight of the parotid gland was reduced by 13%, and the potassium concentration in the parotid gland saliva was increased by 21% (P < 0.05 for all parameters). These results give credence to the validity of the hypothesis which correlates radiation-induced damage of the salivary glands with the injurious role of intracellular redox-active metal ions. Furthermore, the results offer prospects in the clinical setting, as Zn-DFO is a modification of DFO, which is a clinically approved and widely used medication. Further examination of the clinical use of Zn-DFO is currently under way, focusing on its beneficial protective effect on healthy non-neoplastic tissue.

Redox metal chelation ameliorates radiation-induced bone marrow toxicity in a mouse model.

Since zinc desferrioxamine (Zn-DFO) has been shown to be a very potent protector against injuries induced by redox-active metal ions, we examined its protective effect against radiation-induced toxicity. We found that treatment with Zn-DFO given before TBI increased the survival of mice irradiated with 7.5 and 8.5 Gy. Zn-DFO also protected against radiation-induced myelosuppression and body weight loss, while soluble Il6 levels in serum were normalized in mice pretreated with Zn-DFO. We concluded that administration of Zn-DFO prior to TBI protected BALB/c mice from radiation-induced toxicity, increasing survival rates by up to 75%. The biological effect of Zn-DFO is known to result from its effect on the production of intracellular hydroxyl free radicals mediated by redox-active metal ions, and both metal chelation and zinc delivery appear to be equally likely mechanisms for this outcome. We suggest that radiation-induced toxicity is caused by the deleterious effect of redox-active metal ions, and that compounds which modulate this redox activity may act as radioprotectors.

Effects of X irradiation on the function of rat salivary glands at 3 and 40 days.

The purpose of this study was to examine the effects of different doses of X irradiation on the major rat salivary glands. The flow rates of the salivary glands were measured simultaneously in both parotid and submandibular glands of mature male Wistar rats at 3 and 40 days after head and neck irradiation with single doses of 2.5, 5, 7.5, 10, or 15 Gy. The parotid and submandibular glands were weighed at the time of saliva collection and total body weight was obtained weekly. Significant reductions in parotid salivary flow at 3 days and parotid and submandibular flow at 40 days were found. Diminished saliva output was dose-dependent and significantly reduced at radiation exposures of 7.5 Gy and greater. Submandibular function deteriorated between 3 and 40 days and the extent of hypofunction was comparable to the parotid gland at the latter time. Parotid and submandibular gland weights were reduced by irradiation in a dose-dependent manner at both 3 and 40 days. The effects were similar for both glands at the latter time. Total body weight was also reduced by the head and neck irradiation in a dose-dependent manner. There was significant mortality in the group receiving 15 Gy irradiation between 7 and 14 days after irradiation. The results demonstrate that parotid and submandibular glands may be affected comparably by equal doses of head and neck irradiation when examined at later times. In the period immediately after irradiation, there are significant differences in the responses of the major salivary glands.