DNA Damage and Proteomic Profile Changes in Rat Salivary Glands After Chronic Exposure to Inorganic Mercury.

Mercury (Hg) is a toxic metal that became a public health problem due to environmental contamination caused by anthropogenic activity. In this sense, oral homeostasis can undergo changes due to the toxic effects of metal on the salivary glands. Therefore, our objective was to investigate the proteomic and genotoxic changes in salivary glands after exposure to inorganic mercury (IHg). Forty Wistar rats that were divided into a control group, which received distilled water, and an exposed group, which received 0.375 mg/kg of mercury chloride for 45 days via orogastric gavage. After that, the animals were euthanized, and the parotid and submandibular glands were collected for analysis of the genotoxic effects, using the comet assay and proteome global profile assessment. The results showed that IHg promoted damage to cellular DNA associated with proteomic changes that showed events such as oxidative stress, mitochondrial dysfunction, changes in the cytoskeleton, and apoptosis. Therefore, these findings show a profile of molecular changes due to the interactions of IHg with several proteins and mechanisms inherent to the cell, which consequently may result in dysfunction of the salivary glands and impaired homeostasis of the oral cavity.

Effects of Fluoride on Submandibular Glands of Mice: Changes in Oxidative Biochemistry, Proteomic Profile, and Genotoxicity.

Although fluoride (F) is well-known to prevent dental caries, changes in cell processes in different tissues have been associated with its excessive exposure. Thus, this study aimed to evaluate the effects of F exposure on biochemical, proteomic, and genotoxic parameters of submandibular glands. Twenty one old rats (n = 30) were allocated into three groups: 60 days administration of drinking water containing 10 mgF/L, 50 mgF/L, or only deionized water (control). The submandibular glands were collected for oxidative biochemistry, protein expression profile, and genotoxic potential analyses. The results showed that both F concentrations increased the levels of thiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH) and changed the proteomic profile, mainly regarding the cytoskeleton and cellular activity. Only the exposure to 50 mgF/L induced significant changes in DNA integrity. These findings reinforce the importance of continuous monitoring of F concentration in drinking water and the need for strategies to minimize F intake from other sources to obtain maximum preventive/therapeutic effects and avoid potential adverse effects.

Copy Number Alterations in Papillary Thyroid Carcinomas: Does Loss of SESN2 Have a Role in Age-related Different Prognoses?

BACKGROUND/AIM: Thyroid cancer is the only tumor in which age is an important prognostic factor. In papillary thyroid carcinomas (PTC), 45 years of age seems to be a key point that divides adult patients into two groups, with different clinical features. The aim of the study was to perform a microarray-based analysis in two groups of patients (<45 and ≥45 years old), in order to verify the occurrence of specific copy number alterations (CNAs) that could be associated to different patient behaviors associated with age. PATIENTS AND METHODS: In order to search and compare genomic alterations that may be related to age, we evaluated the occurrence of CNAs in the genome of 24 PTC samples, divided in two groups (<45 and ≥45 years old). RESULTS: We identified only one region showing a statistically significant difference between the groups (p=0.00357): a deletion of approximately 537 kps in 1p35.3., which was more frequent in patients aged 45 years or older. This is the region where, among others, the gene SESN2 is located, which is activated under oxidative stress and plays an antioxidant role, in addition to protecting the genetic material from damage generated by reactive oxygen species (ROS). CONCLUSION: This is the first time that a CNA involving the deletion of the SESN2 gene is associated with papillary thyroid carcinomas, particularly in patients aged 45 years and older, indicating that this deletion would lead to a more malignant and prominent tumoral behavior associated to a worst prognosis.

Identifying novel genetic alterations in pediatric acute lymphoblastic leukemia based on copy number analysis.

Copy number variations (CNVs) analysis may reveal molecular biomarkers and provide information on the pathogenesis of acute lymphoblastic leukemia (ALL). We investigated the gene copy number in childhood ALL by microarray and select three new recurrent CNVs to evaluate by real-time PCR assay: DMBT1, KIAA0125 and PRDM16 were selected due to high frequency of CNVs in ALL samples and based on their potential biological functions in carcinogenesis described in the literature. DBMT1 deletion was associated with patients with chromosomal translocations and is a potential tumor suppressor; KIAA0125 and PRDM16 may act as an oncogene despite having a paradoxical behavior in carcinogenesis. This study reinforces that microarrays/aCGH is it is a powerful tool for detection of genomic aberrations, which may be used in the risk stratification.