Exposure to real-ambient bedroom light at night delayed circadian rhythm in healthy Chinese young adults: A cross-sectional study.

BACKGROUND: Light at night (LAN) have attracted increased research attention on account of its widespread health hazards. However, the underlying mechanism remains unknown. The objective of this study was to investigate the effects of real-ambient bedroom LAN exposure on circadian rhythm among young adults and potential sex differences. METHODS: Bedroom LAN exposure was measured at 60-s intervals for 2 consecutive days using a portable illuminance meter. Circadian phase was determined by the dim light melatonin onset (DLMO) time in 7 time-series saliva samples. RESULTS: The mean age of the 142 participants was 20.7 ± 0.8 years, and 59.9% were women. The average DLMO time was 21:00 ± 1:11 h, with men (21:19 ± 1:12 h) later than women (20:48 ± 1:07 h). Higher level of LAN intensity (LANavg ≥ 3lx vs. LANavg < 3lx) was associated with an 81.0-min later in DLMO time (95% CI: 0.99, 1.72), and longer duration of nighttime light intensity ≥ 5lx (LAN5; LAN5 ≥ 45 min vs. LAN5 < 45 min) was associated with a 51.6-min later in DLMO time (95% CI: 0.46, 1.26). In addition, the delayed effect of LAN exposure on circadian phase was more pronounced in men than in women (all P-values <0.05). CONCLUSIONS: Overall, bedroom LAN exposure was significantly associated with delayed circadian rhythm. Additionally, the delayed effect is more significant in men. Keeping bedroom dark at night may be a practicable option to prevent circadian disruption and associated health implications. Future studies with more advanced light measurement instrument and consensus methodology for DLMO assessment are warranted.

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.

Protective Effect of Alpha-Lipoic Acid on Salivary Dysfunction in a Mouse Model of Radioiodine Therapy-Induced Sialoadenitis.

Radioiodine (RI) therapy is known to cause salivary gland (SG) dysfunction. The effects of antioxidants on RI-induced SG damage have not been well described. This study was performed to investigate the radioprotective effects of alpha lipoic acid (ALA) administered prior to RI therapy in a mouse model of RI-induced sialadenitis. Four-week-old female C57BL/6 mice were divided into four groups (n = 10 per group): group I, normal control; group II, ALA alone (100 mg/kg); group III, RI alone (0.01 mCi/g body weight, orally); and group IV, ALA + RI (ALA at 100 mg/kg, 24 h and 30 min before RI exposure at 0.01 mCi/g body weight). The animals in these groups were divided into two subgroups and euthanized at 30 or 90 days post-RI treatment. Changes in salivary 99mTc pertechnetate uptake and excretion were tracked by single-photon emission computed tomography. Salivary histological examinations and TUNEL assays were performed. The 99mTc pertechnetate excretion level recovered in the ALA treatment group. Salivary epithelial (aquaporin 5) cells of the ALA + RI group were protected from RI damage. The ALA + RI group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Fewer apoptotic cells were observed in the ALA + RI group compared to the RI only group. Pretreatment with ALA before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction.

Oral Candida colonization in xerostomic postradiotherapy head and neck cancer patients.

OBJECTIVES: To evaluate (a) oral colonization of Candida species, especially for non-albicans Candida species (NACS), in xerostomic postradiotherapy head and neck cancer patients and (b) risk factors affecting their colonization. MATERIALS AND METHODS: Subjective and objective dry mouth scores, stimulated salivary flow rates, pH and buffering capacity were measured in 72 xerostomic postradiotherapy head and neck cancer patients. Candida counts and species identification were performed using oral rinse samples cultured in Candida Chromagar, followed by polymerase chain reaction and API 20C AUX system. RESULTS: Candida colonization was observed in 87.5% of subjects, with 80.6% and 48.6% of study population colonized by C. albicans and NACS, respectively. NACS was associated with high objective dry mouth scores, denture use, and females (p = .006, .009, and .036, respectively). In addition, Candida glabrata was detected more in females (p = .018) and denture wearers (p = .026), while Candida tropicalis was associated with high objective dry mouth scores (p = .022) and females (p = .027). Quantity of Candida colonization correlated positively with objective dry mouth scores (r = 0.599, p < .001) and negatively with salivary flow rates (r = -0.258, p = .041) and pH (r = -0.290, p = .022). CONCLUSION: NACS colonization was common in xerostomic head and neck cancer patients. Increased signs of dry mouth, female and dental prostheses may promote NACS colonization.

Salivary evaluation in radioactive I131 treated patients with thyroid carcinoma.

BACKGROUND AND OBJECTIVE: radioiodine treatment (I131) used to treat thyroid carcinomas produces side effects (sialadenitis, xerostomia, dysphagia and caries susceptibility) reflecting in a poor patient quality of life. This study aimed to evaluate the effect of I131 on salivary function and possible oral impairment. MATERIAL AND METHODS: Thirty-seven patients undergoing I131 were submitted to oral examination, answer questions regarding xerostomia/hyposalivation and collect saliva at three moments (M1: 30-45 days before I131, M2: 1-2 days after I131 and M3: 7-10 days after treatment). Saliva was assayed for flow rate and calcium/phosphate concentrations. RESULTS AND CONCLUSIONS: significant difference in calcium/phosphate concentration was shown between M1 and M2, with evident decrease at M2. Flow rate reduced right after treatment with 41% of patients returning to previous rate at M3 (no statistical difference). A higher number of patients related xerostomia and difficulty in swallowing food at M2. The results showed that xerostomia/hyposalivation, dysphagia and calcium/phosphate concentration decrease may be considered early radioiodine side effects.

The Effect of Radiotherapy for Treatment of Head and Neck Cancer on Oral Flora and Saliva.

PURPOSE: Radiotherapy causes xerostomia in patients treated for head and neck cancer. This study investigated changes in quality and quantity of saliva after radiotherapy and possible associations between these changes and alterations in oral flora. MATERIALS AND METHODS: The study was a prospective cohort study of patients receiving radiotherapy for head and neck cancer. Suitable patients were recruited before treatment commenced, and informed consent was obtained. Patients were examined, and provided unstimulated and stimulated saliva samples. Quantity of saliva, buffering capacity and pH were measured. Oral flora was cultured from the saliva samples. Oral clearance of glucose and of lactose was measured. These interventions were repeated at intervals after radiotherapy had been completed. RESULTS: Eighteen patients were recruited. Stimulated and unstimulated saliva flow rates, glucose clearance, salivary pH and buffering capacity were significantly reduced after radiotherapy. Candida albicans counts were significantly increased. These increases were significantly correlated with reductions in stimulated and unstimulated salivary flow rates. Counts of lactobacilli, Streptococcus mutans and Bifidobacteriaceae increased, but not statistically significantly. CONCLUSIONS: Therapeutic radiotherapy significantly reduced the quality and quantity of saliva in head and neck cancer patients. These reductions were associated with increased C. albicans counts.

The effect of parotid gland-sparing intensity-modulated radiotherapy on salivary composition, flow rate and xerostomia measures.

OBJECTIVES: To describe parotid gland (PG) saliva organic and inorganic composition and flow rate changes, after curative intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), and analyse the relationship between PG saliva analytes and xerostomia measures. METHODS AND MATERIALS: Twenty-six patients recruited to five prospective phase 2 or 3 trials which assessed toxicity and efficacy of IMRT by HNC subsite, provided longitudinal PG saliva. Salivary flow rate, and subjective and objective xerostomia measures were prospectively collected and saliva tested for inorganic and organic analytes. Statistical comparisons of longitudinal analyte changes and analysis for a relationship between dichotomized xerostomia score and saliva analytes were performed. RESULTS: One hundred and forty-two PG saliva samples from 26 patients were analysed. At 3-6 months after IMRT, stimulated and unstimulated saliva showed significantly decreased flow rate, total protein (TP) secretion rate, phosphate concentration and increased lactoferrin (LF) concentration. Stimulated saliva alone had elevated LF secretion rate and beta-2-microglobulin (B2 M) concentration with decreased calcium (Ca2+ ) and magnesium (Mg2+ ) concentrations and Ca2+ secretion rate. At >12 months, under stimulated and unstimulated conditions, increased LF concentration and decreased Mg2+ and phosphate concentration persisted and, in stimulated saliva, there was decreased potassium (K+ ) and Mg2+ concentration. Unstimulated TP secretion rate was lower in the presence of high-grade xerostomia. Otherwise, no relationship between xerostomia grade and PG salivary flow rate, TP and Ca2+ secretion rate was found. CONCLUSION: Fewer significant differences in PG saliva analytes >12 months after IMRT indicate good functional recovery. Residual xerostomia after IMRT will only be further reduced by addressing the sparing of subsites of the PG or other salivary gland tissues, in addition to the PG.

Oral complications at 6 months after radiation therapy for head and neck cancer.

OBJECTIVE: To examine oral complications 6 months after modern radiation therapy (RT) for head and neck cancer (HNC). METHODS: Prospective multicenter cohort study of patients with HNC receiving intensity-modulated radiation therapy or more advanced RT. Stimulated whole salivary flow, maximal mouth opening, oral mucositis, oral pain, oral health-related quality of life (OH-QOL), and oral hygiene practices were measured in 372 subjects pre-RT and 216 subjects at 6 months from the start of RT. RESULTS: Mean stimulated whole salivary flow declined from 1.09 to 0.47 ml/min at 6 months (p < .0001). Mean maximal mouth opening reduced from 45.58 to 42.53 mm at 6 months (p < .0001). 8.1% of subjects had some oral mucositis at 6 months, including 3.8% with oral ulceration. Mean overall pain score was unchanged. OH-QOL was reduced at 6 months, with changes related to dry mouth, sticky saliva, swallowing solid foods, and sense of taste (p ≤ .0001). At 6 months, there was greater frequency of using dental floss and greater proportion using supplemental fluoride (p < .0001). CONCLUSIONS: Despite advances in RT techniques, patients with HNC experience oral complications 6 months after RT, with resulting negative impacts on oral function and quality of life.

A clinical trial of a novel emulsion for potential use as a saliva substitute in patients with radiation-induced xerostomia.

Researchers have recently developed a novel oily formulation for potential use as a saliva substitute for the treatment of dry mouth. The aim of this randomised, crossover study was to compare this new formulation to a currently available saliva substitute and a control of water on measures of mastication, subjective feeling of oral dryness and product acceptability. Forty participants treated with radiotherapy to the head and neck and experiencing xerostomia were invited to participate in the trial. Each participant trialled all three products in a randomised order. The effect of each product was measured using the Test of Masticating and Swallowing Solids (TOMASS), the Shortened Xerostomia Inventory (SXI) and a questionnaire designed to test patient acceptability of each product. Outcome data were gathered in a single session after the first administration of each product to evaluate immediate effects and after 7 days of use to evaluate longer-term effects. Statistical analyses consisted of repeated-measures analysis of variance and mixed models. There was no evidence that application of the three formulations had an effect on any of the TOMASS measures, either immediately or after one week of use (P > 0·05). There was a significant main effect of formulation on the SXI score (P = 0·02). Application of the novel emulsion resulted in a clinically small but significant improvement in SXI score (P < 0·01); however, application of methylcellulose (P = 0·21) and water (P = 0·81) resulted in no significant difference. There was no difference in participant acceptability between the three products (P = 0·32). The novel oily emulsion showed no clinically significant benefit over two existing products for relief of xerostomia. Indeed, none of the three products demonstrated significant change in patient outcomes.

Home dim light melatonin onsets with measures of compliance in delayed sleep phase disorder.

The dim light melatonin onset (DLMO) assists with the diagnosis and treatment of circadian rhythm sleep disorders. Home DLMOs are attractive for cost savings and convenience, but can be confounded by home lighting and sample timing errors. We developed a home saliva collection kit with objective measures of light exposure and sample timing. We report on our first test of the kit in a clinical population. Thirty-two participants with delayed sleep phase disorder (DSPD; 17 women, aged 18-52 years) participated in two back-to-back home and laboratory phase assessments. Most participants (66%) received at least one 30-s epoch of light >50 lux during the home phase assessments, but for only 1.5% of the time. Most participants (56%) collected every saliva sample within 5 min of the scheduled time. Eighty-three per cent of home DLMOs were not affected by light or sampling errors. The home DLMOs occurred, on average, 10.2 min before the laboratory DLMOs, and were correlated highly with the laboratory DLMOs (r = 0.93, P < 0.001). These results indicate that home saliva sampling with objective measures of light exposure and sample timing, can assist in identifying accurate home DLMOs.

Radiotherapy-induced xerostomia, pre-clinical promise of LMS-611.

PURPOSE: Radiotherapy-induced xerostomia (RIX) is the most common permanent side effect of radiotherapy (RT) to the head and neck (H&N). There is no effective topical treatment. LMS-611 is a mimetic of a natural lamellar body which prevents thick secretions like saliva from congesting organs. The primary objective of this study was to assess saliva properties before and during RT to the H&N. The secondary objectives were to re-assess saliva properties with the addition of LMS-611, measure inter-patient variability, correlate patient-reported symptoms with laboratory measurements and design subsequent first-in-human clinical trial of LMS-611. METHODS: Patients with H&N cancer receiving RT as primary treatment were recruited. Patients completed the Groningen RIX (GRIX) questionnaire and provided saliva samples at baseline and weeks 2, 4 and 6 of RT. Saliva adhesiveness and viscosity were tested by measuring time taken to travel 5 cm down an inclined plane. RESULTS: Thirty patients were enrolled. The inclined plane test (IPT) results (s) were as follows: baseline 31.3, week 2 49.7, week 4 51.1 and week 6 55.7. Wide inter-patient variability was seen at baseline. GRIX scores increased as RT progressed. Spearman rank correlation coefficient of inclined plane tests with GRIX scores was -0.06 at baseline, 0.25 at week 2, 0.12 at week 4 and 0.08 at week 6. LMS-611 concentrations of 10 and 20 mg/ml significantly reduced IPT times on saliva samples. CONCLUSIONS: Saliva becomes more visco-adhesive and RIX worsens as RT progresses. There is little correlation between objective and subjective measures of RIX. The addition of LMS-611 to thick, sticky saliva restores its fluidity ex vivo. This warrants in vivo analysis of the effect of LMS-611 upon RIX.

Toward a more patient-specific model of post-radiotherapy saliva secretion for head and neck cancer patients.

BACKGROUND: Reduction of saliva secretion is a common side effect following radiotherapy (RT) for cancer of the head and neck region. The aim of this study is to predict the post-RT salivary function for individual patients prior to treatment and to recognise possible differences in individual radiosensitivity. MATERIAL AND METHODS: A predictive model for post-RT salivary function was validated for 64 head and neck cancer patients. The input parameters for the model were salivary excretion fraction (sEF) measured by 99mTc-pertechnetate scintigraphy, total stimulated salivary flow and mean absorbed dose for the major salivary glands. SEF values after RT relative to the baseline before RT (rEF) were compared among the patients using the distance ΔrEF between single gland rEF and the corresponding expected value at the dose response curve. RESULTS: A significant correlation (R = 0.86, p = 0.018) was found between the modelled and the measured values of stimulated salivary flow six months after RT. The average prediction error for the saliva flow rate was 6 ml/15 min. A linear relationship between ΔrEF for the left and the right parotid glands was observed both six (R = 0.53) and 12 (R = 0.79) months after RT. The average of absolute values of ΔrEF was 0.20 for parotid glands and 0.22 for submandibular glands. CONCLUSIONS: The salivary flow model was validated for 64 patients. The results imply, that one explanation for the discrepancies between the predicted and the measured salivary flow rate values and the common variations found in ΔrEF for the parotid glands may be differences in patients' individual response to radiation. However, quantitative extraction of individual radiosensitivity would require further studies in order to take it into account in predictive models.

Evaluation of selected biochemical parameters in the saliva of young males using mobile phones.

The biochemical status in the saliva of 12 males before/after using mobile phone has been evaluated. Radio frequency signals of 1800 MHz (continuous wave transmission, 217 Hz modulate and Global System for Mobile Communications [GSM - non-DTX]) with 1.09 w/kg specific absorption rate (SAR) value were used for 15 and 30 min. Cell phone radiation induced a significant increase of superoxide dismutase (SOD); there was a statistically significant effect of talking time on the levels of SOD, F(2, 33) = 8.084, p < 0.05, ω = 0.53. The trend analysis suggests a significant quadratic trend, F(1, 33) = 4.891, p < 0.05; indicating that after 15 min of talking the levels of SOD increased, but as talking time increased the SOD activity started to drop. In contrast to this, there was no statistically significant effect of talking time on the level of salivary albumin, cytochrome c, catalase or uric acid. Results suggest that exposure to electromagnetic radiation may exert an oxidative stress on human cells as evidenced by the increase in the concentration of the superoxide radical anion released in the saliva of cell phone users.

AdLTR2EF1α-FGF2-mediated prevention of fractionated irradiation-induced salivary hypofunction in swine.

Patients frequently experience a loss of salivary function following irradiation (IR) for the treatment of an oral cavity and oropharyngeal cancer. Herein, we tested if transfer of fibroblast growth factor-2 (FGF2) cDNA could limit salivary dysfunction after fractionated IR (7.5 or 9 Gy for 5 consecutive days to one parotid gland) in the miniature pig (minipig). Parotid salivary flow rates steadily decreased by 16 weeks post-IR, whereas blood flow in the targeted parotid gland began to decrease ~3 days after beginning IR. By 2 weeks, post-IR salivary blood flow was reduced by 50%, at which point it remained stable for the remainder of the study. The single preadministration of a hybrid serotype 5 adenoviral vector encoding FGF2 (AdLTR2EF1a-FGF2) resulted in the protection of parotid microvascular endothelial cells from IR damage and significantly limited the decline of parotid salivary flow. Our results suggest that a local treatment directed at protecting salivary gland endothelial cells may be beneficial for patients undergoing IR for oral cavity and oropharyngeal cancer.

The impact of dairy consumption on salivary inoculum.

Quantitative levels of harmful oral microbes present following complex surgical excisions of head and neck cancer are important since wounds are often contaminated through direct connection to the oral cavity and its flora. This possibility is especially important in irradiated patients who have decreased protective salivary function. In addition, high oral microbial levels increase and intensify oral mucositis leading to significant morbidity in patients treated with radiation therapy. One previously untested surgical teaching to decrease the bacterial inoculum present in the oral cavity is to counsel patients against consuming otherwise nutritious dairy products, as they are thought to coat the oral cavity with rate-limiting nutrients vital for bacterial growth. This risk may extend to individuals with chronic laryngeal penetration or aspiration, since salivary bacterial load might represent a lethal threat in the presence of marginal pulmonary reserve. A crossover study using six healthy adult volunteers and six patients who had previously undergone radiation therapy to an oropharyngeal primary site was performed. Saliva samples were quantitatively cultured in both groups with and without the consumption of dairy products at 1-h and 5-h intervals. Analysis of quantitative cultures demonstrated that the consumption of dairy products had no influence on bacterial levels present in previously radiated subjects and nonirradiated controls. Additionally, the consumption of dairy did not affect the composition of microbes present. Due to the lack of changes in both quantity and composition of oral bacteria seen in this study, patients would not benefit from the avoidance of dairy products.

Assessment of oxidant/antioxidant status in saliva of cell phone users.

Hazardous health effects resulting from exposure to radiofrequency electromagnetic radiation (RF-EMR) emitted from cell phones have been reported in the literature. However, the cellular and molecular targets of RF-EMR are still controversial. The aim of this study was to examine the oxidant/antioxidant status in saliva of cell phone users. Saliva samples collected before using a cell phone as well as at the end of 15 and 30 min calls were tested for two commonly used oxidative stress biomarkers: malondialdehyde (MDA) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-Oxo-dG). The 8-oxo-dG levels were determined by enzyme-linked immunosorbent (ELISA) competitive assay, while the MDA levels were measured using the OxiSelect MDA adduct ELISA Kit. The antioxidant capacity of the saliva was evaluated using the oxygen radical absorption capacity (ORAC) and the hydroxyl radical averting capacity (HORAC) assays according to the manufacture instructions. The mean 8-oxo-dG and the Bradford protein concentrations (ng/ml and mg/ml, respectively) peaked at 15 min. The levels of HORAC, ORAC and MDA progressively increased with time and reached maximum at 30 min. However, there was no significant effect of talking time on the levels of 8-OxodG and MDA. Similarly, there was no statistically significant effect of talking time on the oxygen and hydroxyl radicals averting capacities, (ORAC) and (HORAC), respectively. These findings suggest that there is no relationship between exposure to radio frequency radiation (RFR) and changes in the salivary oxidant/antioxidant profile.

Radiation-associated changes in saliva composition of head and neck cancer patients: A systematic review.

Xerostomia is a common radiation-associated toxicity in patients with head and neck cancer. Although several studies examined the decrease in saliva production due to radiotherapy (RT) and investigated the factors associated with this side effect, little is known about the change in radiation-associated saliva composition. This systematic review is the first to summarize existing data and give an overview of the change in pH/buffer capacity, electrolytes, proteins, enzymes, and mucins due to radiation to the salivary glands. Literature search was performed in PubMed and Embase with 47 articles finally eligible for the review, analyzing the saliva composition at several time points before, during and/or after RT, or comparing findings in irradiated patients to a healthy control group. Overall, RT leads to a substantial decrease in salivary pH and buffer capacity. For sodium, chloride and calcium ion, as well as amylase, an increased concentration or activity during RT was reported in most of the studies, followed by a subsequent decrease either already during RT or after the end of treatment. Different trends have been described for the total protein concentration during and after RT. Lactoferrin, however, increased considerably, especially in the first phase of RT. Mucin 5B (MUC5B) concentrations showed a slight increase during RT and concentrations around baseline values again six months post-radiotherapy.

Applicability of Gene Expression in Saliva as an Alternative to Blood for Biodosimetry and Prediction of Radiation-induced Health Effects.

As the great majority of gene expression (GE) biodosimetry studies have been performed using blood as the preferred source of tissue, searching for simple and less-invasive sampling methods is important when considering biodosimetry approaches. Knowing that whole saliva contains an ultrafiltrate of blood and white blood cells, it is expected that the findings in blood can also be found in saliva. This human in vivo study aims to examine radiation-induced GE changes in saliva for biodosimetry purposes and to predict radiation-induced disease, which is yet poorly characterized. Furthermore, we examined whether transcriptional biomarkers in blood can also be found equivalently in saliva. Saliva and blood samples were collected in parallel from radiotherapy (RT) treated patients who suffered from head and neck cancer (n = 8) undergoing fractioned partial-body irradiations (1.8 Gy/fraction and 50-70 Gy total dose). Samples were taken 12-24 h before first irradiation and ideally 24 and 48 h, as well as 5 weeks after radiotherapy onset. Due to the low quality and quantity of isolated RNA samples from one patient, they had to be excluded from further analysis, leaving a total of 24 saliva and 24 blood samples from 7 patients eligible for analysis. Using qRT-PCR, 18S rRNA and 16S rRNA (the ratio being a surrogate for the relative human RNA/bacterial burden), four housekeeping genes and nine mRNAs previously identified as radiation responsive in blood-based studies were detected. Significant GE associations with absorbed dose were found for five genes and after the 2nd radiotherapy fraction, shown by, e.g., the increase of CDKN1A (2.0 fold, P = 0.017) and FDXR (1.9 fold increased, P = 0.002). After the 25th radiotherapy fraction, however, all four genes (FDXR, DDB2, POU2AF1, WNT3) predicting ARS (acute radiation syndrome) severity, as well as further genes (including CCNG1 [median-fold change (FC) = 0.3, P = 0.013], and GADD45A (median-FC = 0.3, P = 0.031)) appeared significantly downregulated (FC = 0.3, P = 0.01-0.03). A significant association of CCNG1, POU2AF1, HPRT1, and WNT3 (P = 0.006-0.04) with acute or late radiotoxicity could be shown before the onset of these clinical outcomes. In an established set of four genes predicting acute health effects in blood, the response in saliva samples was similar to the expected up- (FDXR, DDB2) or downregulation (POU2AF1, WNT3) in blood for up to 71% of the measurements. Comparing GE responses (PHPT1, CCNG1, CDKN1A, GADD45A, SESN1) in saliva and blood samples, there was a significant linear association between saliva and blood response of CDKN1A (R2 = 0.60, P = 0.0004). However, the GE pattern of other genes differed between saliva and blood. In summary, the current human in vivo study, (I) reveals significant radiation-induced GE associations of five transcriptional biomarkers in salivary samples, (II) suggests genes predicting diverse clinical outcomes such as acute and late radiotoxicity as well as ARS severity, and (III) supports the view that blood-based GE response can be reflected in saliva samples, indicating that saliva is a "mirror of the body" for certain but not all genes and, thus, studies for each gene of interest in blood are required for saliva.

The influence of parotid gland sparing on radiation damages of dental hard tissues.

OBJECTIVE: The aim of the present study was to evaluate whether radiation damage on dental hard tissue depends on the mean irradiation dose the spared parotid gland is subjected to or on stimulated whole salivary flow rate. MATERIAL AND METHODS: Between June 2002 and October 2008, 70 patients with neck and cancer curatively irradiated were included in this study. All patients underwent dental treatment referring to the guidelines and recommendations of the German Society of Dental, Oral and Craniomandibular Sciences prior, during, and after radiotherapy (RT). During the follow-up period of 24 months, damages on dental hard tissues were classified according to the RTOG/EORTC guidelines. The mean doses (D(mean)) during spared parotid gland RT were determined. Stimulated whole saliva secretion flow rates (SFR) were measured before RT and 1, 6, 12, 24 months after RT. RESULTS: Thirty patients showed no carious lesions (group A), 18 patients developed sporadic carious lesions (group B), and 22 patients developed general carious lesions (group C). Group A patients received a D mean of 21.2 ± 11.04 Gy. Group B patients received a D(mean) of 26.5 ± 11.59 Gy and group C patients received a D(mean) of 33.9 ± 9.93 Gy, respectively. The D(mean) of group A was significantly lower than the D(mean) of group C (p < 0.001). Additionally, the mean SFR 6 months after RT of group A was significantly higher than the mean SFR of group C (p < 0.01). CONCLUSIONS: Irradiation damage on dental hard tissue correlates with increased mean irradiation doses as well as decreased salivary flow rates. CLINICAL RELEVANCE: Parotid gland sparing resulting in a dose below 20 Gy reduces radiation damage on dental hard tissues, and therefore, the dose may act as a predictor for the damage to be expected.

Effect of ultraviolet C radiation on biological samples.

AIM: To examine the influence of ultraviolet C (UVC) radiation on blood, saliva, semen, and naked DNA samples for preventing DNA cross-contamination on working surfaces in laboratories. METHODS: Blood, saliva, semen, and DNA isolated from buccal swab samples were obtained from a single male donor and applied to the laboratory working surfaces. UVC radiation was applied to these diluted and undiluted samples with or without previous decontamination of the working surfaces with 10% sodium hypochlorite and 20% ethanol. Genomic DNA was extracted using Chelex. After quantification, DNA was amplified using the AmpFlSTR® NGM™ PCR Amplification Kit. We tested and statistically analyzed DNA concentration, UVC dose, sample volume, radiation time, the number of correctly detected alleles on genetic loci, and the number of correctly detected alleles in four groups in which 16 loci were divided. RESULTS: When working surfaces were not decontaminated and were treated only with UVC radiation in the laboratory, the genetic profile for naked DNA could not be obtained after 2 minutes of UVC radiation and for saliva after 54 hours. For blood and semen, a partial genetic profile was obtained even after 250 hours of UVC radiation in the laminar. When working surfaces were decontaminated with 10% sodium hypochlorite and 20% ethanol, genetic profile could not be obtained for naked DNA after 2 minutes, for saliva after 4 hours, for blood after 16 hours, and for semen after 8 hours of UVC radiation in the laboratory. CONCLUSION: It is recommended to carefully and thoroughly clean working surfaces with 10% sodium hypochlorite and 20% ethanol followed by minimal 16-hour UVC exposure (dose approximately 4380 mJ/cm2) for complete and successful decontamination.