Effect of smoking on MUC1 expression in oral epithelial dysplasia, oral cancer, and irradiated oral epithelium.

OBJECTIVES: The aim of this study was to assess the MUC1 expression in the oral epithelium of normal, oral epithelial dysplasia (OED), oral squamous cell carcinoma (OSCC), and irradiated oral epithelium (IROE) and its association with smoking habits in non-smokers and smokers. DESIGN: Oral mucosal biopsies from controls, OED, OSCC, and IROE groups were obtained and categorized based on the smoking history as non-smokers, smoker I (25 pack-years), and smoker II (>25 pack-years). Immunohistochemical staining of MUC1 using human milk fat globule 1 (HMFG 1) antibody was performed, and the MUC1 score was calculated. The relation between MUC1 expression and clinicopathological findings was examined. RESULTS: MUC1 staining of superficial oral epithelial cells with mild MUC1 score was detected in all control samples. The MUC1 staining extended from superficial to basal cell layer of oral epithelium with the increase in MUC1 score from moderate to strong in OED, OSCC, and IROE, and the difference was significant (p < 0.004, p < 0.002 and p < 0.004, respectively) compared to controls. A positive association between smoking and MUC1 score was observed within groups (p < 0.05). CONCLUSION: The depolarization of MUC1 protein expression is associated with smoking habits in OED and OSCC. In the IROE, the radiation causes subcellular and molecular changes, observed as altered MUC1 expression and accelerated by smoking, furthermore, complicating the oral mucosal adaptation and progress to radiation-induced lesions as a delayed effect.

Head and neck radiotherapy leading to extensive late oral soft-tissue necrosis.

Radiotherapy is generally used as an adjuvant treatment in malignant head and neck tumors, which can cause a series of toxicities to tissues involved in the radiation field. Hard tissue necrosis surrounding the tumor is widely debated and recognized; however, oral mucosa necrosis as a late effect of head and neck radiotherapy is a toxicity that has been little explored and understood in the literature. The present report describes a 53-year-old Caucasian, diabetic man with a painful yellowish mass in the buccal mucosa, remaining oral mucositis with history of radiotherapy completed 90 days ago as adjuvant treatment for a polymorphic adenocarcinoma in the palate. Photobiomodulation was used as therapy for tissue necrosis with good therapeutic response despite discontinuation of treatment by the patient. Since there are few descriptions and illustrations of radiotherapy-related soft tissue necrosis, the current case may bring some new experience with this important topic, which directly impacts on the patient's quality of life.

Reirradiation Using 198Au Grain Brachytherapy for Recurrent Oral Cancer Cases Previously Treated by Definitive Radiotherapy.

BACKGROUND/AIM: We investigated treatment outcomes and complications during reirradiation of patients with oral cancers. PATIENTS AND METHODS: Six patients who received definitive radiotherapy for oral cancer as the initial treatment and brachytherapy for recurrence were included. Local control and overall survival rates, soft tissue and mandibular complications, and tooth extraction were investigated. RESULTS: The five-year local control and overall survival rates were 83.3% and 100%, respectively. The occurrence rate of grade 2 soft tissue and mandible complications was 33.3%, and the primary sites were the buccal mucosa and the floor of mouth. The positions of the extracted tooth in the two cases were adjacent to the tumor, and one case developed grade 2 complication of the mandible. CONCLUSION: During recurrence of the buccal mucosa and the floor of mouth cancers, reirradiation should be avoided considering mandibular complications. To avoid reirradiation-related complications, tooth extraction near the radiation field should be avoided.

The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies.

Oral mucositis (OM) is a common, highly symptomatic complication of cancer therapy that affects patients' function, quality of life, and ability to tolerate treatment. In certain patients with cancer, OM is associated with increased mortality. Research on the management of OM is ongoing. Oral mucosal toxicities are also reported in targeted and immune checkpoint inhibitor therapies. The objective of this article is to present current knowledge about the epidemiology, pathogenesis, assessment, risk prediction, and current and developing intervention strategies for OM and other ulcerative mucosal toxicities caused by both conventional and evolving forms of cancer therapy.

Safety and efficacy of Oro-T oral rinse in oral mucositis during cancer radiotherapy and/or chemotherapy: Cumulative analysis of two studies.

INTRODUCTION: Oral mucositis is inflammation of the mucosa of the mouth which ranges from redness to severe ulceration. It results from the local effects of radiation to the oral mucosa. OBJECTIVES: The study is cumulative analysis of two studies (one comparative and the other open labeled) evaluated in individuals with oral mucositis during cancer radiotherapy and/or chemotherapy for the safety and efficacy of Oro-T mouthwash in a comparative design with normal saline. METHODOLOGY: Both the studies were similar with respect to clinical and laboratory parameters for analysis. The participants were advised to use 10 ml of Oro-T for 1 min 4 times daily for 6 weeks starting from day 1 of standard care. Patients were followed up, and the results were assessed from baseline on visit days: At entry and at the end of every week for 6 weeks. Clinical assessment of oral condition was done objectively (by the investigator) and also subjectively. Clinical symptoms such as sore throat, number of ulcer, burning sensation, pain, difficulty in chewing, difficulty in drinking, and mucositis grading along with Patient Reported Outcome Measures Scale were evaluated at each interval. Data was available for 40 subjects in Oro-T and 15 subjects in NS groups respectively. RESULTS AND CONCLUSION: The significant positive outcome was reported both subjectively and objectively in Oro-T group as compared to NS group with the delay in the onset of symptoms and less severe manifestation of oral mucositis with an improvement in quality of life. No adverse effects were reported that prompted discontinuation of study medication. Overall compliance to study medication was good.

Fluorescent spectroscopic assessment before and after radiation treatment in oral cavity cancer and its clinical correlation.

BACKGROUND: Biochemical changes in irradiated malignant tissue lead to altered autofluorophores status which should be different for cancerous tissue (residual/recurrence) and irradiated normal tissue. If this irradiated tissue is examined through fluorescent spectroscopy, we can find the spectroscopic changes occurring after the completion of treatment which can be helpful in evaluating treatment response. METHODS: Punch biopsy sample was examined through fluorescent spectroscopy in oral cavity cancer patients before and after definitive radiation treatment. The change in spectroscopic pattern before and after radiation treatment was recorded and assessed. RESULTS: Final analysis was done in 36 samples. In irradiated tissue, it has been observed that there was increase in the intensity of collagen fluorescence. It was found that the Half width half maximum (HWHM) is more in case of preirradiated sample. The decrease in the HWHM in case of irradiated sample shows the decrease in the number of cells (cell density as compared to that in preirradiated sample). These spectral findings are well-explained pathophysiologically and clinically as amount of collagen are increased in irradiated tissues due to loss of cancerous cells and regeneration of collagen cross-links (fibrosis) and reproduction of normal tissue as a response to radiation treatment. CONCLUSION: After thorough study in a large number of samples, we may be able in the future to grade the alteration in fluorescence of collagen obtained after radiation treatment in terms of complete, partial, or no response.

Noncoplanar Versus Coplanar Intensity-Modulated Radiation Therapy (IMRT) for Protection of the Lip and Buccal Mucosa.

OBJECTIVE: In this study, by comparing coplanar and noncoplanar intensity-modulated radiation therapy (IMRT) treatment planning in treating tongue cancer, the significance of noncoplanar fields in the protection of the lip and buccal mucosa was determined, and a reasonable solution was selected. METHODS: Forty-eight tongue cancer patients treated from June 2019 to February 2021 were selected and randomly divided into a coplanar field group and a noncoplanar field group. The mucosal dose limit changed from 15 Gy to 45 Gy for comparison of the two treatment plans. The evaluation indicators (conformal index (CI); homogeneity index (HI); D5, D50, and D98 of the target volume; and the dose of normal tissues) were calculated under different mucosal dose limits. The clinical observation of the lip and buccal mucosa of 48 cases was monitored and graded carefully according to NCI-CTCAE V4.0. Statistical analyses were performed. RESULTS: The differences in CI, HI, D98, D50 and D5 between the two groups in the target volume tended to decrease when the mucosal dose limit was less than 30 Gy, with a significant difference (P < 0.05). When the limit exceeded 30 Gy, significant differences in other indicators except CI (P < 0.05) were still noted. In normal tissue, differences in doses between the two groups existed when the mucosal limit was less than 20 Gy, with a significant difference (P < 0.05). When the limit exceeded 20 Gy, no significant difference was noted. Patients in the noncoplanar group showed significantly better results than those in the other group in terms of the radiation-related toxicity of the lip and cheek membrane(P < 0.001). CONCLUSIONS: Compared with coplanar field radiotherapy, noncoplanar field radiotherapy can effectively reduce the exposure dose to the lip and buccal mucosa. The application of noncoplanar treatment plans exhibits good clinical significance and deserves to be promoted.

Transitions in oral and gut microbiome of HPV+ oropharyngeal squamous cell carcinoma following definitive chemoradiotherapy (ROMA LA-OPSCC study).

BACKGROUND: Oral and gut microbiomes have emerged as potential biomarkers in cancer. We characterised the oral and gut microbiomes in a prospective observational cohort of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) patients and evaluated the impact of chemoradiotherapy (CRT). METHODS: Saliva, oropharyngeal swabs over the tumour site and stool were collected at baseline and post-CRT. 16S RNA and shotgun metagenomic sequencing were used to generate taxonomic profiles, including relative abundance (RA), bacterial density, α-diversity and ß-diversity. RESULTS: A total of 132 samples from 22 patients were analysed. Baseline saliva and swabs had similar taxonomic composition (R2 = 0.006; p = 0.827). Oropharyngeal swabs and stool taxonomic composition varied significantly by stage, with increased oral RA of Fusobacterium nucleatum observed in stage III disease (p < 0.05). CRT significantly reduced the species richness and increased the RA of gut-associated taxa in oropharyngeal swabs (p < 0.05), while it had no effect in stool samples. These findings remained significant when adjusted by stage, smoking status and antibiotic use. CONCLUSIONS: Baseline oral and gut microbiomes differ by stage in this HPV+ cohort. CRT caused a shift towards a gut-like microbiome composition in oropharyngeal swabs. Stage-specific features and the transitions in oral microbiome might have prognostic and therapeutic implications.

Oral health-related quality of life in oral cancer patients: systematic review and meta-analysis.

Aim: The purpose of this meta-analysis was to evaluate the impact of oral health on quality of life in oral cancer patients (OCPs). Methods: PubMed, Scopus and Web of Science databases were searched for publications on oral health-related quality of life (OHRQoL) in OCP and the information was extracted according to the PRISMA guidelines. A random effect model was used to obtain the pooled standard mean differences of Oral Health Impact Profile (OHIP)-14 questionnaire responses in meta-analysis. Results: total of 12 research papers were analyzed and revealed poor OHRQoL in OCPs (standard mean difference: 2.53; 95% CI: 1.55-3.50; p < 0.00001) compared with healthy individuals due to the effects of oncotherapy. Moreover, OHRQoL deteriorated with combinations of different treatment modalities. Conclusion: Oral health and oncotherapy can affect the quality of life in OCPs.

Low-frequency electromagnetic field influences human oral mucosa keratinocyte viability in response to lipopolysaccharide or minocycline treatment in cell culture conditions.

The aim of the current study was to investigate the influence of low-frequency electromagnetic field (LF-EMF) exposure on viability parameters of oral mucosa keratinocytes cultured in in vitro conditions. The effect of LF-EMF stimulation on cell viability was also specified in the simultaneous presence of lipopolysaccharide (LPS) infectious agent or minocycline (Mino) anti-inflammatory agent. Viability parameters such as early-, late apoptosis and necrosis of keratinocytes were analysed by the flow cytometry method (FCM). The exposure of human oral keratinocyte cell cultures to LF-EMF acting alone or combined with LPS/minocycline agents caused changes in the percentage of cells that undergo programmed or incidental cell death. The overall obtained results are compiled in a graphical form presented in Fig. 1.

Effects of an elemental diet, Elental®, may differ between healthy oral cells and oral cancer cells.

The effectiveness of an elemental diet (ED), Elental®, against radiotherapy­ or chemoradiotherapy­induced oral mucositis was previously reported. However, the administration of additional nutrition or an ED in patients with oral cancer may also provide extra nutrition for cancer cells, which could result in cancer development. At present, it remains unclear whether the beneficial effects of an ED are likely to surpass its potential harmful effects on oral cancer treatment. In the present study, we aimed to clarify whether Elental® has different effects on a healthy human oral keratinocyte (HOK) cell line compared with its effects on oral squamous cell carcinoma (OSCC) cell lines (HSC2, HSC3, HSC4). The efficacy of Elental® was compared in relation to the growth and migration ability of HOK and OSCC cell lines using MTT assay and migration assay, respectively. In addition, whole transcriptome analysis and network analysis were performed to determine the difference in the mechanism of action of Elental® between HOK and HSC2 cells. In addition, Elental® promoted growth and migration ability of­malnourished and 5­fluorouracil (5­FU)­treated damaged HOK cells cultured in low nutrition medium (0% growth supplement). However, Elental® did not affect the growth ability of 5­FU­treated damaged HSC2 cell line in low nutrition medium (0 or 1% fetal bovine serum (FBS), as well as the growth ability of HSC3 and HSC4 cell lines in medium containing 0% FBS. Elental® pre­treatment also enhanced the apoptosis­inducing effect of anticancer agents against OSCC cells. In addition, whole transcriptome analysis and Ingenuity Pathways Analysis (IPA) data suggested that Elental® may help in the proliferation and survival of HOK through the induction of ERK. Moreover, Elental® added stress to HSC2 cells through the induction of the endoplasmic reticulum stress response marker, BiP and GRP 94. The results showed that Elental® may add stress to HSC2 cells and provide growth stimulation to HOK. These findings suggest that the effects of Elental® on healthy oral cells and oral cancer cells may differ.

Molecular effects of photon irradiation and subsequent aftercare treatment with dexpanthenol-containing ointment or liquid in 3D models of human skin and non-keratinized oral mucosa.

This study aimed to investigate the molecular effects of radiation and subsequent aftercare treatment with dexpanthenol-containing ointment and liquid on established full-thickness 3D skin models depicting acute radiodermatitis and mucositis. To mimic radiomucositis and radiodermatitis, non-keratinized mucous membrane and normal human skin models were irradiated with 5 Gray. Afterwards, models were treated topically every second day with dexpanthenol-containing ointment or liquid in comparison with placebo and untreated controls. On day 7 after irradiation, histological examination showed impairments in irradiated models. In contrast, models treated with dexpanthenol-containing ointment or liquid showed a completely restored epidermal part. While gene expression profiling revealed an induction of genes related to a pro-inflammatory milieu, oxidative stress and an impaired epidermal differentiation after irradiation of the models, aftercare treatment with dexpanthenol-containing ointment or liquid revealed anti-oxidative and anti-inflammatory effects and had a positive effect on epidermal differentiation and structures important for physical and antimicrobial barrier function. Our findings confirm the potential of our established models as in vitro tools for the replacement of pharmacological in vivo studies regarding radiation-induced skin injuries and give indications of the positive effects of dexpanthenol-containing externals after radiation treatments as part of supportive tumor treatment.

Assessment and prevalence of concomitant chemo-radiotherapy-induced oral mucositis in patients with oral squamous cell carcinoma

Background/aim: Quantification of oral mucositis that progresses during concomitant chemo-radiotherapy (CCRT) is essential for its management. It is important to determine the methods that are simple, reliable and beneficial in foreseeing mucositis at earlier stages of treatment. Materials and methods: A prospective study was conducted on 100 oral cancer patients receiving CCRT following the inclusion criteria. Patients were evaluated for mucositis i.e. erythema and ulcers by using the World Health Organization (WHO) scale and the oral mucositis assessment scale (OMAS), whereas mature and immature cells were identified by exfoliative cytology. Clinical examination and procedure of oral cavity were performed before, on days 5, 17, and at the end of treatment. Results: Oral mucositis was observed in all oral squamous cell carcinoma (OSCC) patients receiving CCRT on different days with noteworthy increase from day 5 of CCRT to the end of treatment. For OMAS grading related to ulceration and erythema, Grade 1 (7.2%; 34%) was most commonly seen on the 5th day of CCRT, Grade 2 (29%; 19%) and Grade 3 (19%) were most frequently seen at the 17th day and end of CCRT, accordingly. With respect to WHO scale grades 1 and 2 (18.3%; 21.5%) was most frequently observed at the 17th day of CCRT, whereas grades 3 and 4 (12.5%; 2%) was noted at the end of CCRT. There was statistically significant increase in the percentage of immature cells at the end of CCRT (99%). A significant association (P < 0.0000) was observed among the days of smear and maturation stages of epithelial cells as well as among WHO mucositis grading, OMAS and types of epithelial cells, respectively. Conclusion: According to the findings of the study, oral mucositis grade is directly proportional to the progressing days of CCRT. Oral mucositis is frequently related to adverse clinical outcomes, affecting the patient's quality of life. It is essential to develop methods that can be employed for the assessment of CCRT associated oral mucositis.

ODONTOLOGICAL EFFECTS OF IONIZING RADIATION (review). / ODONTOLOGIChNI EFEKTY IONIZUIuChOGO VYPROMINIuVANNIa (ogliad).

BACKGROUND: Odontological effects of ionizing radiation (IR) as a result of radiotherapy, the consequences of accidents at nuclear power plants and industry, individual occupational exposure, etc. deserve significant attention interns of radiation medicine and radiation safety. OBJECTIVE: to analyze and summarize clinical and experimental data on the odontological radiation effects. OBJECT: the pathological changes in the hard tissues of teeth, pulp, periodontium, mucousmembranes of the mouth and jaws due to exposure to IR. METHOD: search in the PubMed / MEDLINE, Google Scholarabstract medical and biological databases, scientific libraries of the relevant sources of scientific information. RESULTS: Radiobiological effects of IR due to its direct and indirect action are manifested throughout the period ofodontogenesis and formation of the facial skeleton. Experimental and clinical data (in children and adults) indicatethe increased risk of dental caries, reduction of pain threshold and vascularization of tooth pulp along with its fibrosis and atrophy, periodontal dysfunction, which predispose to a high probability of tooth loss. Abnormalities in theactivity of osteoblasts and cementoblasts of dental periosteum and osteoblasts of alveolar process in combinationwith circulatory disorders due to endothelial cell death, hyalinization, thrombosis and vascular obliteration increasethe risk of jaw osteoradionecrosis. Children who have undergone a prenatal exposure to IR as a result of theChornobyl NPP accident have a premature change of teeth. Deterioration of periodontal tissues and early development of acute and complicated dental caries are typical for children and adults affected by the Chornobyl disaster. CONCLUSIONS: Summarized data on the effects of radiation exposure under different conditions on teeth primordia(i.e. immature teeth), their formation and eruption in experimental and clinical settings, as well as on the odontological radiation effects in adults are summarized. Condition of the teeth in the Chornobyl NPP accident survivorsis described. Understanding and taking into account the radiobiological odontological effects is necessary in thelight of planning, preparing, and conducting local radiation therapy and developing the standards of radiation safety and measures to protect professionals and the public in the event of possible radiation accidents at the nuclearpower plants and industry facilities.

Butyrylcholinesterase: An economical marker of disease activity in oral squamous cell carcinoma before and after therapy.

INTRODUCTION: Biomarkers which can predict disease progression and serve as prognostic indicators are necessary for better management of oral cancer. Studies have shown that Cholinesterase plays an important role in cellular proliferation, differentiation and may have a possible involvement in tumor growth. AIM AND OBJECTIVE: The present study is aimed to determine the utility of serum Butyrylcholinesterase (BChe) levels as a marker for progression of oral squamous cell carcinoma (OSCC) in relation to the grade of the tumor and to determine if any variation occurred in the levels of BChe before and after therapy. MATERIALS AND METHODS: A total of 120 patients were included in the study and divided into two groups as Group A-30 patients (healthy individuals) and Group B-90 cases of histopathologically diagnosed OSCC. The blood sample was collected before surgery, re-collected after the completion of radiotherapy (i.e., 3 and 6 months postsurgery) and analyzed biochemically for the concentration of BCh. STATISTICAL ANALYSIS: Paired t-test, ANOVA, and post hoc test (Bonferroni) were used for determining the statistical significance. RESULTS: BChe levels were lower in OSCC (2940.32-1405.50 u/l when compared with controls (11149.60-11243.07 unit/l) and this difference was statistically significant. Postoperatively at 3 months, the serum BChe levels of OSCC patients increased almost two-fold compared to the preoperative values, and this difference was also statistically significant (P = 0.000) After 6 months, these levels further increased but did not reach those of controls. CONCLUSION: BChe can be used as an inexpensive, easy to use, noninvasive biomarker for the evaluation of disease-free survival in OSCC patients.

Photobiomodulation modulates inflammation and oral microbiome: a pilot study.

INTRODUCTION: Oral mucositis (OM) is a severe side effect in patients undergoing anticancer therapies, which negatively impacts on their quality of life often leading to either the interruption of the therapy. Photobiomodulation (PBM) is emerging as an effective strategy allowing a faster wound healing. OBJECTIVES: This pilot study aims at verifying whether PBM modulates the inflammatory response in patients and its effect on the oral microbiome composition. MATERIALS AND METHODS: Buccal swabs were collected from four patients affected by OM, both on ulcerated and clinically healthy areas, before and on the last day of PBM therapy, as well as on the first day after treatment discontinuation. The concentration of 38 cytokines and the composition of oral microbiome were measured. RESULTS: Most of the pro-inflammatory cytokines were reduced, whereas anti-inflammatory cytokines resulted up-regulated by PBM. In addition, PBM influenced the composition of oral microbiome, by decreasing the amount of pathogenic species and promoting the growth of commensal bacteria. These changes were even more evident when separately analysing patients who clinically responded to PBM and the only patient who did not respond. CONCLUSIONS: PBM reduces inflammatory burden in patients affected by OM and positively influences the composition of the oral microbiome.

The efficacy of an ayurvedic preparation of yashtimadhu (Glycyrrhiza glabra) on radiation-induced mucositis in head-and-neck cancer patients: A pilot study.

BACKGROUND: Oral mucositis is a common and debilitating painful side effect of many forms of chemotherapy and radiation therapy. Mucositis may lead to dose reductions and unplanned interruptions of chemotherapy and/or radiotherapy (RT) and often affects patients' quality of life. AIM: The objective of the study was to assess the efficacy of the ayurvedic preparation in decreasing the severity of mucositis in head-and-neck cancer patients receiving concomitant chemoradiotherapy. MATERIALS AND METHODS: In this prospective randomized study, the patients were divided into three groups. Group 1 patients received conventional mucositis treatment, whereas Group 2 patients received ayurvedic preparation Yashtimadhu in addition to conventional treatment. Group 3 patients received honey for local application in oral cavity as well as one tea spoon of honey twice daily orally in addition to routine conventional treatment. All the patients were assessed for mucositis at the end of every week during the RT for a period of 6 weeks. RESULTS: A significant difference was observed between the groups at each time point. Nearly 42.85% of patients in conventional treatment arm developed Grade 3 mucositis, 20% of patients developed Grade 3 mucositis in group where honey was given, and only 15.5% of patients developed Grade 3 mucositis in Yastimadhu group. Unplanned treatment breaks and hospitalization of patients were reduced with the use of yashtimadhu as compared to other two groups. CONCLUSION: Yashtimadhu was observed to be effective and delayed the development of severe form of mucositis. The drug appeared to be more efficient in the management of radiation-induced mucositis.

Effects of mobile phone radiation on buccal mucosal cells: A systematic review.

The worldwide increased use of mobile phone in recent years has raised many questions on whether their use is safe to user who is exposed to electromagnetic radiation. The aim of the review is to find out the effect of mobile phone emitted radiations on buccal mucosal cells. To identify suitable literature, an electronic search was performed using PubMed, Trip database, Cochrane, Google Scholar and EBSCO host database. The search was focused on the effect of mobile phone radiation on buccal cells. Among the literature available in English, the screening of the related titles and abstracts was done, and only those articles were selected for full-text reading that fulfilled the inclusion and exclusion criteria. The initial literature search resulted in 23 articles out of which only 7 articles fulfilled the criteria were included in this systematic review. The Studies showed that mobile phone-emitted radiations have adverse effects on buccal mucosal cells such as the formation of micronuclei and broken egg which was considered as bio-markers of genotoxicity.

Protective Effects of N-Acetylcysteine against Radiation-Induced Oral Mucositis In Vitro and In Vivo.

PURPOSE: Radiation-induced oral mucositis limits delivery of high-dose radiation to targeted cancers. Therefore, it is necessary to develop a treatment strategy to alleviate radiation-induced oral mucositis during radiation therapy. We previously reported that inhibiting reactive oxygen species (ROS) generation suppresses autophagy. Irradiation induces autophagy, suggesting that antioxidant treatment may be used to inhibit radiation-induced oral mucositis. MATERIALS AND METHODS: We determined whether treatment with N-acetyl cysteine (NAC) could attenuate radiation-induced buccal mucosa damage in vitro and in vivo. The protective effects of NAC against oral mucositis were confirmed by transmission electron microscopy and immunocytochemistry. mRNA and protein levels of DNA damage and autophagy-related genes were measured by quantitative real-time polymerase chain reaction and western blot analysis, respectively. RESULTS: Rats manifesting radiation-induced oral mucositis showed decreased oral intake, loss of body weight, and low survival rate. NAC intake slightly increased oral intake, body weight, and the survival rate without statistical significance. However, histopathologic characteristics were markedly restored in NAC-treated irradiated rats. LC3B staining of rat buccal mucosa revealed that NAC treatment significantly decreased the number of radiation-induced autophagic cells. Further, NAC inhibited radiation-induced ROS generation and autophagy signaling. In vitro, NAC treatment significantly reduced the expression of NRF2, LC3B, p62, and Beclin-1 in keratinocytes compared with that after radiation treatment. CONCLUSION: NAC treatment significantly inhibited radiation-induced autophagy in keratinocytes and rat buccal mucosa and may be a potentially safe and effective option for the prevention of radiation-induced buccal mucosa damage.

Application of the buccal micronucleus cytome assay on child population exposed to sinus X-ray.

PURPOSE: Diagnostic X-ray examinations of paranasal sinuses use a low-dose ionizing radiation to achieve medically indicated purposes. The effects of low-dose radiation are still controversial, making it a highly prioritized field of research. As there is a need to evaluate the effects of low-dose ionizing radiation and that children might be a more vulnerable population, we performed simultaneous physical dosimetry and buccal cell micronucleus cytome assay on pediatric patients before and after an X-ray examination of the sinuses. METHODS: The study comprised 20 subjects aged 11.9 ± 3.6 years, and BMI < 25 kg/m2. Physical dosimetry was performed using radiophotoluminiscent (RPL) glass dosimeters placed on four positions on the head. The buccal cell micronucleus cytome assay was performed before and 14 ± 1 days after the X-ray exam, to monitor DNA damaging, replicative, cytostatic, and cell death effects. RESULTS: The doses in the primary beam ranged 371-1106 µGy and were several fold higher than at the other positions on the head. As for biological changes, we did not observe any DNA damaging effects. However, a significant increase in cells with condensed chromatin was observed, indicating more cells undergoing early stages of apoptosis. We also observed inter-individual differences between the subjects. A correlation between the doses detected and biological effects was not observed. CONCLUSION: Although we did not observe significant increase in DNA damage, further studies are needed to increase the statistical power of the results and ensure patients' safety and optimal health care.