Deoxyribonucleic Acid Damage Research Articles

8-Hydroxy-2-Deoxyguanosine as Oxidative DNA Damage Biomarker of Medical Ionizing Radiation: A Scoping Review.

Background: Recent studies reported the significant expansion using 8-Hydroxy-2-Deoxyguanosine (8-OHdG) as a biomarker of oxidative Deoxyribonucleic Acid (DNA) damage among human populations exposed to medical ionizing radiation, but a generalized overview about this topic has not been conducted yet. Objective: This scoping review of published literature examined recent trends in utilizing 8-OHdG biomarker to measure oxidative DNA damage induced by medical ionizing radiation and possible factors that may influence the 8-OHdG level.Material and Methods: Literature search was conducted in PubMed, Scopus and ProQuest databases for publications from 1984 to 2/12/2020. Included articles were: cohort studies, case-control studies, and cross–sectional studies, randomized and nonrandomized controlled trials. Excluded articles were: editorials, letters, personal opinions, newspaper articles, study plans, protocols, qualitative studies, case reports and series, in-vivo and vitro studies, animal research studies, reviews and meta-analyses. Results: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we screened 141 articles, and 10 eligible studies met our inclusion criteria. All studies measured 8-OHdG as an oxidative DNA damage biomarker. The study results were contradictory concerning the relationship between the radiation dose and 8-OhdG level. 8-OHdG was mostly measured by enzyme-linked immunosorbent assay (ELISA) using urine samples. Sample size varied between (n=25-230) and included patients who underwent medical radiation procedures or workers exposed to ionizing radiation during their jobs. Conclusion: This scoping review findings showed 8-OHdG can be used as a promising biomarker to detect oxidative damage, resulting from medical ionizing radiation exposure despite external factors that may influence 8-OHdG levels.

Cellular Effects of Ultraviolet-Radiated Reduced-Titanium Dioxide Nanoparticles on Human Hypopharyngeal Adenocarcinoma Cells.

The cellular effects of ultraviolet (UV)-radiated reduced-titanium dioxide (TiO₂) nanoparticles were investigated on human hypopharyngeal adenocarcinoma cells (FaDu). In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the viability of FaDu cells exposed to UV (254 nm) for 10 minutes, in the presence of reduced-TiO₂ nanoparticles in rutile, was dose- and time-dependently decreased. The UV-radiated reduced-TiO₂ suppressed the cell proliferation by inhibiting the expression of cell cycle kinase, cyclin dependent kinase 2 (Cdk2), and its functional regulators Cyclin E and Cyclin B1 as well as proliferation-regulating proteins of p85 regulatory sub-unit of phosphoinositide3-kinases (PI3K p85), phosphorylated protein kinase B (p-AKT/p-PKB) and phosphorylated mammalian target of rapamycin (p-mTOR). In addition, the mitochondria disintegration and deoxyribonucleic acid (DNA) damage were confirmed by detecting the accumulated Bax in cytoplasm, phosphorylated-H2A histone family member X (γ-H2AX) in chromosomes and phosphorylated checkpoint 2 (p-Chk2). Our results support that UV-activated reduced-TiO₂ in rutile sensitized UV-induced proliferation suppression of FaDu cancer cells by the enhanced photocat-alytic activity.

Poly adenosine diphosphate-ribosylation, a promising target for colorectal cancer treatment.

The development of colorectal cancer (CRC) can result from changes in a variety of cellular systems within the tumor microenvironment. Particularly, it is primarily associated with genomic instability that is the gradual accumulation of genetic and epigenetic changes consisting of a characteristic set of mutations crucial for pathways in CRC progression. Based on this background, the potential to focus on poly [adenosine diphosphate (ADP)-ribose] polymerase (PARP)-1 and poly-ADP ribosylation (PARylation) as the main causes of malignant formation of CRC may be considered. One of the important functions of PARP-1 and PARylation is its deoxyribonucleic acid (DNA) repair function, which plays a pivotal role in the DNA damage response and prevention of DNA damage maintaining the redox homeostasis involved in the regulation of oxidation and superoxide. PARP-1 and PARylation can also alter epigenetic markers and chromatin structure involved in transcriptional regulation for the oncogenes or tumor suppressor genes by remodeling histone and chromatin enzymes. Given the high importance of these processes in CRC, it can be considered that PARP-1 and PARylation are at the forefront of the pathological changes required for CRC progression. Therefore, this review addresses the current molecular biological features for understanding the multifactorial function of PARP-1 and PARylation in CRC related to the aforementioned roles; furthermore, it presents a summary of recent approaches with PARP-1 inhibition in non-clinical and clinical studies targeting CRC. This understanding could help embrace the importance of targeting PARP-1 and PARylation in the treatment of CRC, which may present the potential to identify various research topics that can be challenged both non-clinically and clinically.

An evaluation of DNA double strand break formation and excreted guanine species post whole body PET/CT procedure.

Ionizing radiation-induced oxidation and formation of deoxyribonucleic acid (DNA) double strand breaks (DSBs) are considered the exemplar of genetic lesions. Guanine bases are most prone to be oxidized when DNA and Ribonucleic acid (RNA) are damaged. The repair processes that are initiated to correct this damage release multiple oxidized guanine species into the urine. Hence, the excretion of guanine species can be related with the total repair process. Our study quantified the total DSBs formation and the amount of guanine species in urine to understand the DNA break and repair process after whole body (WB) exposure to 18F-FDG positron emission tomography/computed tomography (PET/CT). A total of 37 human participants were included with control and test groups and the average radiation dose was 27.50 ± 2.91 mSv. γ-H2AX foci assay in the collected blood samples was performed to assess the DSBs, and excreted guanine species in urine were analyzed by a competitive ELISA method. We observed a significant increase of DNA damage that correlated well with the increasing dose (p-value 0.009) and body weight (p-value 0.05). In the test group, excreted guanine species in urine sample significantly increased (from 24.29 ± 5.82 to 33.66 ± 7.20 mg/mmol creatinine). A minimum (r2 = 0.0488) correlation was observed between DSBs formation and excreted guanine species. A significant difference of DNA damage and 8-OHdG formation was seen in the test group compared to controls. Larger population studies are needed to confirm these observations, describe the fine-scale timing of changes in the biomarker levels after exposure, and further clarify any potential risks to patients from PET/CT procedures.

Oxidative DNA damage and subclinical hypothyroidism in children with obesity

BackgroundObesity-related oxidation stress plays a key role in obesity complications; however, its relation to thyroid status is an area for further research. The study aimed to assess thyroid function in obese children and its relation to oxidative deoxyribonucleic acid (DNA) damage.ResultsFifty obese and 40 normal weight children were included. Anthropometric measurement, lipid profile, thyroid function, anti-thyroglobulin antibody, thyroid peroxidase antibody, and 8-hydroxydeoxyguanosine serum level as marker of oxidative DNA damage were measured. Thirty-six percent of children with obesity have subclinical hypothyroidism. Central obesity but not oxidative DNA damage and lipid profile was significantly associated with subclinical hypothyroidism. Waist circumference > 97th centile increases the risk for subclinical hypothyroidism (odd ratio 10.82; confidence interval 95% 2.75–42.409; p-value<0.001).ConclusionCentral obesity represents a risk factor for subclinical hypothyroidism in obese children. Oxidation DNA damage did not show significant association with subclinical hypothyroidism.

Studying of the effect of the genetic variant c.470T&gt;C in the CHEK2 gene on increasing the risk of breast cancer in the population of the Russian Federation

Introduction. Currently, there are conflicting data regarding the effect of the c.470T&gt; C germline mutation in the CHEK2 gene on increasing the risk of breast cancer (BC), so it is necessary to conduct research on large samples of patients, including in the Russian population, in order to analyze the contribution of this mutation to the risk of cancer developing.The aim of the study was to determine the frequency of occurrence of the genetic variant c.470Т&gt;С in the CHEK2 gene in the Russian population in patients with BC and patients with benign breast diseases (BBD) to assess the possible effect of this deoxyribonucleic acid damage on the likelihood of cancer occurrence.Materials and methods. The study included 2,787 patients with BC and 1,004 patients with BBD who underwent examination and treatment at the Russian Scientific Center of Roentgenoradiology of the Ministry of the Russian Federation from 2010 to 2018. Molecular genetic study was carried out by real-time polymerase chain reaction to determine the characteristic of the Russian population hereditary genetic variant c.470Т&gt;С in the CHEK2 gene using a diagnostic panel that allows to determine three germline mutations: c.1100delC, c.444+1G&gt;A and c.470Т&gt;С in the CHEK2 gene.Results. In patients with BC the frequency of the mutation c.470T&gt;C in the CHEK2 gene was 3.8 %, in patients with BBD this mutation was detected in 4.7 % of cases. The frequency of the genetic variant c.470T&gt;C in high-risk groups was: 5.1 % – for BC patients with clinical signs of hereditary disease and 4.9 % – for patients with BBD with a family history of cancer. There were no statistically significant differences between the frequency of the mutation c.470T&gt;C in the general groups of BC patients and patients with BBD and the corresponding frequency in the high-risk groups, as well as in the groups of BC patients and patients with BBD (p &gt;0.05).Conclusion. The results of this study indicate the probable absence of a relationship between the presence of the mutation c.470Т&gt;С in the CHEK2 gene and an increased risk of BC.

Potential of HBx Gene for Hepatocarcinogenesis in Noncirrhotic Liver.

Current treatments for hepatitis B virus (HBV) using nucleos(t)ide analogs cannot eliminate the risk of hepatocellular carcinoma (HCC) development. As HBV-associated HCC can develop even in the absence of liver cirrhosis, HBV is regarded to possess direct oncogenic potential. HBV regulatory protein X (HBx) has been identified as a primary mediator of HBV-mediated hepatocarcinogenesis. A fragment of the HBV genome that contains the coding region of HBx is commonly integrated into the host genome, resulting in the production of aberrant proteins and subsequent hepatocarcinogenesis. Besides, HBx interferes with the host DNA or deoxyribonucleic acid damage repair pathways, signal transduction, epigenetic regulation of gene expression, and cancer immunity, thereby promoting carcinogenesis in the noncirrhotic liver. However, numerous molecules and pathways have been implicated in the development of HBx-associated HCC, suggesting that the mechanisms underlying HBx-mediated hepatocarcinogenesis remain to be elucidated.

Efficacy of Coccinia grandis against monosodium glutamate induced hepato-cardiac anomalies by inhibiting NF-kB and caspase 3 mediated signalling in rat model.

Since prehistoric times Coccinia grandis has been used as traditional medicine for various diseases including diabetes, dyslipidemia, metabolic and digestive disorders. Although the rationality of efficacy as natural antioxidants with different bioactive compounds in Coccinia grandis against monosodium glutamate (MSG) induced hepato-cardiac damage remains to be disclosed. Six different solvent extracts of the leaves of Coccinia grandis were chosen to evaluate in vitro antioxidant and free radical (FR)-scavenging activity. Due to high antioxidant content and FR-scavenging property of ethanol extract of Coccinia grandis leaves (EECGL) and presence of different bioactive compounds in EECGL was further tested to evaluate in vivo hepato-protective and cardio-protective efficacy against MSG-induced anomalies. MSG-induced dyslipidemia, increased cell toxicity markers altered functional status and histopathological peculiarities of target organs were blunted by EECGL. Additionally, MSG incited increase level of interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-1β which activates nuclear factor kappa-B (NF-kB) guided inflammation via down regulation of IL-10; impaired redox-homeostasis subsequently promoted inflammation associated oxidative stress (OS) and increased vascular endothelial growth factor (VEGF) which provoked microvascular proliferation related cellular damage. On the contrary, increased lipid peroxidation and nitric oxide promotes reduced cell viability, deoxyribonucleic acid damage and apoptosis via activation of caspase 3. EECGL significantly reduced MSG-induced inflammation mediated OS and apoptosis via inhibition of pro-inflammatory factors and pro-apoptotic mediators to protect liver and heart. Therefore, it can be suggested that EECGL contributed competent scientific information to validate the demands for its use to treat MSG-induced hepato-cardiac OS mediated inflammation and apoptosis from natural origin.

Tauroursodeoxycholic acid/TGR5 signaling promotes survival and early development of glucose-stressed porcine embryos†.

Conditions of impaired energy and nutrient homeostasis, such as diabetes and obesity, are associated with infertility. Hyperglycemia increases endoplasmic reticulum stress as well as oxidative stress and reduces embryo development and quality. Oxidative stress also causes deoxyribonucleic acid damage, which impairs embryo quality and development. The natural bile acid tauroursodeoxycholic acid reduces endoplasmic reticulum stress and rescues developmentally incompetent late-cleaving embryos, as well as embryos subjected to nuclear stress, suggesting the endoplasmic reticulum stress response, or unfolded protein response, and the genome damage response are linked. Tauroursodeoxycholic acid acts via the Takeda-G-protein-receptor-5 to alleviate nuclear stress in embryos. To evaluate the role of tauroursodeoxycholic acid/Takeda-G-protein-receptor-5 signaling in embryo unfolded protein response, we used a model of glucose-induced endoplasmic reticulum stress. Embryo development was impaired by direct injection of tauroursodeoxycholic acid into parthenogenetically activated oocytes, whereas it was improved when tauroursodeoxycholic acid was added to the culture medium. Attenuation of the Takeda-G-protein-receptor-5 precluded the positive effect of tauroursodeoxycholic acid supplementation on development of parthenogenetically activated and fertilized embryos cultured under standard conditions and parthenogenetically activated embryos cultured with excess glucose. Moreover, attenuation of tauroursodeoxycholic acid/Takeda-G-protein-receptor-5 signaling induced endoplasmic reticulum stress, oxidative stress and cell survival genes, but decreased expression of pluripotency genes in parthenogenetically activated embryos cultured under excess glucose conditions. These data suggest that Takeda-G-protein-receptor-5 signaling pathways link the unfolded protein response and genome damage response. Furthermore, this study identifies Takeda-G-protein-receptor-5 signaling as a potential target for mitigating fertility issues caused by nutrient excess-associated blastomere stress and embryo death.

English

In this case report we discuss a patient with neurological manifestations thought to be a case of hepatic encephalopathy. With no improvement in symptoms despite treatment, it created a diagnostic dilemma. Eventually, toxicological investigations were done which revealed that heavy metal poisoning could be the possible culprit. Encephalopathy is characterised by impaired mental state as a result of a diffuse brain dysfunction or other psychiatric condition that induces unconsciousness, typically followed by diffuse electroencephalogram (EEG) anomalies. Both primary neurological and systemic disorders are root causes of encephalopathy. Encephalopathy results from several causes such as liver failure or liver cancer, metabolic abnormalities, anoxic encephalopathy, infections, exposure to harmful compounds such as lithium paint, synthetic contaminants (toxins), inflammations (systemic lupus erythematous, sarcoidosis), drug induced, demyelination (e.g., multiple sclerosis), degenerative process like Alzheimer disease, Parkinson disease and hereditary encephalopathies such as leukodystrophy of the white matter. 1 Humans have used heavy metals since many years. While many harmful health effects of heavy metals have long been established, exposure to heavy metals continues to rise in some parts of the world, especially in underdeveloped countries. Emissions have decreased over the past 100 years in most developed countries. Heavy metals are prevalent and remain in the ecosystem, in general causing bio amplification. Living systems frequently associate with heavy metals in different proportions in the habitat. Heavy metal exposure induces lipid peroxidation, Deoxyribonucleic Acid (DNA) damage and protein modification by generation of oxygen free radicals. Exposure to these metals occurs in occupational areas by equipment, air, food and drinking water. Prolonged exposure to heavy metals may lead to neurotoxicity and brain damage. When symptoms of toxic encephalopathy emerge immediately following single acute exposure to high levels of toxic chemicals it is termed as acute toxic encephalopathy. Other than that if symptoms emerge insidiously over time in association with repeated or chronic exposure to low levels of neurotoxins it is called as chronic toxic encephalopathy. 2 In some cases, diagnosis of toxic encephalopathy is complicated by the fact that toxic chemicals can also damage liver and kidneys. In these cases hepatic dysfunction must be successfully treated before diagnosis of toxic encephalopathy can be considered. It is a diagnosis of exclusion, so a full work up for other possible aetiologies such as hepatic, uremic and infectious should be done. In this case report we have discussed heavy metal encephalopathy masquerading as hepatic dysfunction.

Targeting epigenetic alterations in the treatment of glioma

A glioma is a kind of tumor that initiates in the glial cells of the brain or the spinal cord. High rates of complications and mortality are leading features of gliomas, a glioma can be treated through a surgical procedure, radiation, and chemotherapy. This short communication aimed to analyze the crucial role of epigenetic alterations in the pathogenesis of gliomas and the possible treatment of gliomas by manipulating epigenetic mechanisms. The pathogenesis of glioma is associated with key epigenetic mechanisms, which are deoxyribonucleic acid (DNA) methylation, abnormal microribonucleic acid (RNA), chromatin remodeling, and histone modifications. Alterations and mutations in genes are often seen in gliomas. Alterations and mutations in isocitrate dehydrogenase 1 (IDH1) are commonly found in gliomas; mutant IDH1 facilitates the maintenance of genomic stability in tumors by increasing the DNA damage reaction. Moreover, therapeutic modification of epigenetic alterations connected with the development of gliomas is of utmost clinical significance; comprehensive knowledge of epigenetic aberrations that lead to the formation of glioma will help in the design and development of epigenetic drugs for the treatment of gliomas. Some medications that target epigenetic alterations such as inhibitors of mutant IDH, bromodomain and extraterminal motif inhibitors, histone deacetylase inhibitor, DNA methylation inhibitors, and enhancer of zeste homolog 2 inhibitors are presently used to tackle glioma.

Lung adenocarcinoma concomitant with xeroderma pigmentosum: a case report

BackgroundXeroderma pigmentosum is a rare, autosomal-recessive photosensitive dermatosis. Patients with xeroderma pigmentosum have an impaired ability to repair deoxyribonucleic acid damage caused by ultraviolet rays, resulting in skin cancer. Patients with xeroderma pigmentosum are more susceptible to some cancers. We herein report a case of xeroderma pigmentosum accompanied by lung cancer.Case presentationThe patient was a Japanese woman in her 70s with a family history of consanguineous marriage. Her medical history included squamous cell carcinoma and basal cell carcinoma, in addition to xeroderma pigmentosum. She presented with dry skin with small, pigmented spots, which were particularly focused around the areas exposed to sunlight. Chest computed tomography was conducted to assess for any evidence of metastatic skin carcinoma, and revealed a tumor in the left upper subpleural lobe of the lung. Consequently, she was referred to our department. Finally, we diagnosed lung adenocarcinoma (pT2aN0M1b: stage IVA). She had an epidermal growth factor receptor (EGFR) mutation (p.L858R). Treatment with an epidermal growth factor receptor tyrosine kinase inhibitor (gefitinib) was initiated, and the tumor gradually regressed. No side effects were observed. However, she later died from aspiration pneumonia.ConclusionsAlthough xeroderma pigmentosum is rare, a history of consanguineous marriage should be verified. Because of the severe side effects of cisplatin and radiotherapy in xeroderma pigmentosum patients, the risks and benefits of treatment should be considered thoroughly.

Elevated Serum Reactive Oxygen Species Level Predicts Early Abortion

Background: Impaired trophoblast invasion is associated with early abortion. The calorie needed for the trophoblast cell (TC) invasion is mainly met by adenosine triphosphate (ATP) produced in the mitochondria. Reactive oxygen species (ROS), byproduct of ATP synthesis, plays an important role in cellular physiology, but a high level of ROS may result in deoxyribonucleic acid (DNA) damage or cell dysfunction, thereby impaired TC invasion leading to early abortion. The study aims to determine elevated serum ROS level to predicts early abortion.Materials and method: This was an observational study with a cross-sectional design. Fifty subjects with gestational age less than 12 weeks, consist of 25 early abortions and 25 normal pregnancies subjects, were included in this study. Clinical examination and diagnosis are carried out in 2 Hospitals and 5 Public Health Centers in Padang. Examination of ROS levels was carried out by enzyme-linked immunosorbent assay (ELISA) in the Biomedical Laboratory, Faculty of Medicine, Universitas Andalas. The Mann-Whitney test was used to analyze the difference of serum ROS levels, with a significance level of 0.05.Results: The subjects of the two study groups were equivalent in terms of age, gestational age, and gravidity (p=0.051, p=0.453, and p=1.000). The median ROS levels were found to be 1.36 (1.02-26.30) ng/mL in the early abortion and 1.20 (0.43-2.75) ng/mL in the normal pregnancy (p=0.003).Conclusion: There is a significant difference between ROS levels in early abortion and normal pregnancy.Keywords: ROS, early abortion, normal pregnancy

Pulmonary alveolar stem cells undergo senescence, apoptosis and differentiation by p53-dependent and -independent mechanisms in telomerase deficient mice.

Pulmonary senescence and fibrosis occur with deoxyribonucleic acid (DNA) damage response in the lungs deficient of telomerase. The molecular mechanism mediating pulmonary alveolar cell fates remains to be investigated. The present study shows that pulmonary alveolar epithelial type 2 cells (AEC2) (alveolar stem cells) undergo not only replicative senescence, but also apoptosis and differentiation in association with increased innate immune natural killer (NK) cells in telomerase knockout (KO) mice. Telomerase ribonucleic acid (RNA) component (TERC) deficiency results in increased senescence-associated heterochromatin foci marker HP1γ, p21, p16 and apoptosis-associated cleaved caspase-3 in AEC2. However, p53 deficiency in the Trp53-/- allele of the late generation of TERC KO mice attenuates the increased senescent and apoptotic markers significantly. Moreover, p53 deficiency has no significant effect on the increased gene expression of T1α (a marker of terminal differentiated alveolar epithelial type 1 cells [AEC1]) in AEC2 of the late generation of TERC KO mice. Collectively, our findings suggest that pulmonary senescence takes place in deficiency of telomerase RNA component with the alveolar stem cells undergoing p53-dependent senescence and apoptosis as well as p53-independent differentiation.

Scientific rationale of hospital discharge as a sustainable source of irrigation water: Detection, phytological assessment and toxicity verification

Hospital discharge (HD) represents the primary point source of pharmaceutical components that may constitute not only a sharp risk of phytotoxic effects in food crops, but leaving behind the toxicity implications to the environment. The present work has been oriented to the scientific assessment of pharmaceutical compounds in HD. The phenological, physiological, and morphological changes, oxidative stress biomarkers, antioxidative responses, bioaccumulation and bioconcentration factor in relation to different concentrations of HD-induced irrigation in Ipomoea aquatica were evaluated; while the cytotoxicity and genotoxicity on human hepatocellular carcinoma (HepG2) cell were assessed. Acetaminophen, metoprolol, atenolol, enalapril, and metformin were predominantly detected in the raw HD and bioaccumulated in I. aquatica. Concentration-dependent phenological inhibition, chlorophylls reductions, morphological distortions, reactive oxygen species generation, and antioxidant enzymes upregulation were recorded in the HD-irrigated I. aquatica. Drastic reductions in cell viability and increase of tail damage and tail moment indicated the metabolic alterations of mitochondrial function, and deoxyribonucleic acid (DNA) damage via oxidative stress and DNA adducts formation in the HD-treated groups. The diluted HD at 5% and 10 % could be feasibly reused for food crops irrigation, verified by the negligible phytotoxic implications in the plant model, bioaccumulation, and cytotoxic and genotoxic effects in HepG2 cell.

DNA Electrochemical Biosensors for In Situ Probing of Pharmaceutical Drug Oxidative DNA Damage.

Deoxyribonucleic acid (DNA) electrochemical biosensors are devices that incorporate immobilized DNA as a molecular recognition element on the electrode surface, and enable probing in situ the oxidative DNA damage. A wide range of DNA electrochemical biosensor analytical and biotechnological applications in pharmacology are foreseen, due to their ability to determine in situ and in real-time the DNA interaction mechanisms with pharmaceutical drugs, as well as with their degradation products, redox reaction products, and metabolites, and due to their capacity to achieve quantitative electroanalytical evaluation of the drugs, with high sensitivity, short time of analysis, and low cost. This review presents the design and applications of label-free DNA electrochemical biosensors that use DNA direct electrochemical oxidation to detect oxidative DNA damage. The DNA electrochemical biosensor development, from the viewpoint of electrochemical and atomic force microscopy (AFM) characterization, and the bottom-up immobilization of DNA nanostructures at the electrode surface, are described. Applications of DNA electrochemical biosensors that enable the label-free detection of DNA interactions with pharmaceutical compounds, such as acridine derivatives, alkaloids, alkylating agents, alkylphosphocholines, antibiotics, antimetabolites, kinase inhibitors, immunomodulatory agents, metal complexes, nucleoside analogs, and phenolic compounds, which can be used in drug analysis and drug discovery, and may lead to future screening systems, are reviewed.

PprI: The Key Protein in Response to DNA Damage in Deinococcus.

Deoxyribonucleic acid (DNA) damage response (DDR) pathways are essential for maintaining the integrity of the genome when destabilized by various damaging events, such as ionizing radiation, ultraviolet light, chemical or oxidative stress, and DNA replication errors. The PprI–DdrO system is a newly identified pathway responsible for the DNA damage response in Deinococcus, in which PprI (also called IrrE) acts as a crucial component mediating the extreme resistance of these bacteria. This review describes studies about PprI sequence conservation, regulatory function, structural characteristics, biochemical activity, and hypothetical activation mechanisms as well as potential applications.

Mutational signatures associated with exposure to carcinogenic microplastic compounds bisphenol A and styrene oxide.

Microplastic pollutants in oceans and food chains are concerning to public health. Common plasticizing compounds Bisphenol-A (BPA) and Styrene-7,8-Oxide (SO) are now labeled as carcinogens. We show that BPA and SO cause deoxyribonucleic acid damage and mutagenesis in human cells, and analyze the genome-wide point mutation and genomic rearrangement patterns associated with BPA and SO exposure. A subset of the single- and doublet base substitutions shows mutagenesis near or at guanine, consistent with these compounds’ preferences to form guanosine adducts. Presence of other mutational signatures suggest additional mutagenesis probably due to complex effects of BPA and SO on diverse cellular processes. Analyzing data for 19 cancer cohorts, we find that tumors of digestive and urinary organs show relatively high similarity in mutational profiles, and the burden of such mutations increases with age. Even within the same cancer type, proportions of corresponding mutational patterns vary among the cohorts from different countries, as does the amount of microplastic waste in ocean waters. BPA and SO are relatively mild mutagens, and other environmental agents can also potentially generate similar, complex mutational patterns in cancer genomes. Nonetheless, our findings call for systematic evaluation of public health consequences of microplastic exposure worldwide.

Assessment of DNA Damage in Chick Embryo Brains Exposed to 2G and 3G Cell Phone Radiation using Alkaline Comet Assay Technique

Introduction: The cellular phones/mobile phones have emerged as the fastest growing man-made phenomenon ever discovered in the history. Controversies still exist among the scientific community regarding the ill-effects of Radiofrequency Radiation (RFR) exposure from cell phones on biological tissues. The present study will provide an insight into the basic mechanisms by which RF fields interact with developing brain in an embryo. Aim: To assess the possible Deoxyribonucleic Acid (DNA) damage in developing brain of chick embryo following chronic exposure to Ultra-High Frequency/Radiofrequency Radiation (UHF/RFR) emitted from 2G and 3G cell phone. Materials and Methods: Fertilised hen eggs were divided into three groups. Experimental Group A (exposed to 2G radiation, 24 eggs), Experimental Group B (exposed to 3G radiation, 24 eggs) and Group C sham exposed control group (24 eggs). After the completion of scheduled duration of exposure (72 minutes per day), the chick embryos were sacrificed from 9th-12th day and the brains were dissected out. The chick embryo brains were then subjected to alkaline comet assay technique to assess the DNA damage. The results were statistically compared using one-way Analysis of Variance (ANOVA). Results: In the present study, the exposure of chick embryo brains to 2G and 3G cell phone radiation caused increased mean comet length (p&lt;0.001), mean tail length (p&lt;0.001), mean percentage of DNA in the tail (p&lt;0.001) and mean tail moment (p&lt;0.01) suggestive of increased DNA damage. Conclusion: The present study concludes that the RFR exposure caused significant increase in DNA damage in developing brain of chick embryos with changes more pronounced in 3G exposure group.

Interplay between oxidative stress, SIRT1, reproductive and metabolic functions.

Silent information Regulators (SIRT1) gene stimulates antioxidants’ expression, repairs cells damaged by oxidative stress (OS), and prevents the cells’ dysfunction. In particular, the role of different Sirtuins, particularly SIRT1 in reproduction, has been widely studied over the past decade. Decreased SIRT 1 causes mitochondrial dysfunction by increasing Reactive Oxygen Species (ROS), lipid peroxidation, and DNA damage in both male and female gametes (Sperms and Oocytes), leading to infertility. In the female reproductive system, SIRT1 regulates proliferation and apoptosis in granulosa cells (GCs), and its down-regulation is associated with a reduced ovarian reserve. SIRT1 also modulates the stress response to OS in GCs by targeting a transcription factor vital for ovarian functions and maintenance.ROS-mediated damage to spermatozoa’s motility and morphology is responsible for 30–80% of men’s infertility cases. High levels of ROS can cause damage to deoxyribo nucleic acid (DNA) in the nucleus and mitochondria, lipid peroxidation, apoptosis, inactivation of enzymes, and oxidation of proteins in spermatozoa. SIRT 1 is a cardioprotective molecule that prevents atherosclerosis by modulating various mechanisms such as endothelial injury due to impaired nitric oxide (NO) production, inflammation, OS, and regulation of autophagy. SIRT 1 is abundantly expressed in tubular cells and podocytes. It is also found to be highly expressed in aquaporin 2 positive cells in the distal nephron suggesting its involvement in sodium and water handling. SIRT1 improves insulin resistance by reducing OS and regulating mitochondrial biogenesis and function. It also decreases adiposity and lipogenesis and increases fatty acid oxidation. So, its involvement in the multiple pathways ensures its unique role in reproductive and metabolic derangement mechanisms.