Molecular mechanisms of cadmium induced mutagenicity

2006 ◽  
Vol 25 (2) ◽  
pp. 67-77 ◽  
Author(s):  
M Filipič ◽  
T Fatur ◽  
M Vudrag
Keyword(s):  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Test System ◽  
Dna Lesions ◽  
Regulatory Agencies ◽  
Exogenous Dna ◽  
Cancer Initiation ◽  
Long Time ◽  
Cell Test ◽  
Strong Mutagen

Cadmium is a human carcinogen of worldwide concern because it accumulates in the environment due to its extremely long half-life. Its compounds are classified as human carcinogens by several regulatory agencies. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities and can cause numerous molecular lesions that would be relevant to carcinogenesis. For a long time cadmium has been considered as a non-genotoxic carcinogen, as it is only weakly mutagenic in bacterial and mammalian cell test systems. Recently, we presented evidence that when assayed in a test system, in which both intragenic and multilocus mutations can be detected, cadmium acts as a strong mutagen which induces predominantly multilocus deletions. In this review, we discuss two mechanisms that play an important role in cadmium mutagenicity: (i) induction of reactive oxygen species (ROS); and (ii) inhibition of DNA repair. Experimental evidence suggests that cadmium at low, for environmental exposure relevant concentrations, induces mutations by inducing oxidative DNA damage and that it decreases genetic stability by inhibiting the repair of endogenous and exogenous DNA lesions, which in turn increase the probability of mutations and consequently cancer initiation by this metal.

scholarly journals ‘Liver let die’: oxidative DNA damage and hepatotropic viruses

2014 ◽  
Vol 95 (5) ◽  
pp. 991-1004 ◽  
Author(s):  
Martin R. Higgs ◽  
Philippe Chouteau ◽  
Hervé Lerat
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cellular Response ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Large Body ◽  
Clinical Importance ◽  
Dna Lesions ◽  
Chronic Infections ◽  
The Impact

Chronic infections by the hepatotropic viruses hepatitis B virus (HBV) and hepatitis C virus (HCV) are major risk factors for the development of hepatocellular carcinoma (HCC). It is estimated that more than 700 000 individuals per year die from HCC, and around 80 % of HCC is attributable to HBV or HCV infection. Despite the clear clinical importance of virus-associated HCC, the underlying molecular mechanisms remain largely elusive. Oxidative stress, in particular DNA lesions associated with oxidative damage, play a major contributory role in carcinogenesis, and are strongly linked to the development of many cancers, including HCC. A large body of evidence demonstrates that both HBV and HCV induce hepatic oxidative stress, with increased oxidative DNA damage being observed both in infected individuals and in murine models of infection. Here, we review the impact of HBV and HCV on the incidence and repair of oxidative DNA damage. We begin by giving a brief overview of oxidative stress and the repair of DNA lesions induced by oxidative stress. We then review in detail the evidence surrounding the mechanisms by which both viruses stimulate oxidative stress, before focusing on how the viral proteins themselves may perturb the cellular response to oxidative DNA damage, impacting upon genome stability and thus hepatocarcinogenesis.

Urtica dioica in the Management of Benign Prostate Hyperplasia (BPH)

2020 ◽  
Vol 10 (5) ◽  
pp. 535-542
Author(s):  
Mohaddese Mahboubi
Keyword(s):  
Molecular Mechanisms ◽  
Life Quality ◽  
Urtica Dioica ◽  
Urinary Flow ◽  
Prostate Hyperplasia ◽  
Long Time ◽  
Tract Infections ◽  
Preclinical And Clinical Studies ◽  
Benign Prostate ◽  
Maximum Urinary Flow

Background:: Benign Prostatic hyperplasia (BPH) is known as a disease prevalent in men after the age of 50 years old. Ninety percent of men with the age of 80 years and over have BPH. BPH is associated with functional problems like dysuria, nocturia, polyuria, urinary incontinence and recurrent urinary tract infections. Urtica dioica or nettle is a popular medicinal plant for management of BPH in men. Objective:: This article evaluates the efficacy and safety of nettle and its related possible mechanisms in the management of BPH. Methods:: For the preparation of this manuscript, all the information was gathered from accessible and inaccessible resources (Web, Books, Thesis, etc.). Results:: The results of preclinical and clinical studies confirmed the efficacy of nettle roots extracts (methanol, ethanol, and petroleum ether) in the improvement of BPH in term of IPSS score, and patient's life quality. An increase in mean and maximum urinary flow rates and a reduction in prostate volume and residual urine level were observed after treatment with nettle extract. Nettle roots should be used for 6-12 months as its use is possible for a long time without any serious adverse effects. Conclusion:: Designing the clinical trials to compare the efficacy of different extracts from roots or leaves and investigation of molecular mechanisms of action could be the approaches for future.

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

scholarly journals Immunomodulatory Effects of Radiotherapy

2020 ◽  
Vol 21 (21) ◽  
pp. 8151
Author(s):  
Sharda Kumari ◽  
Shibani Mukherjee ◽  
Debapriya Sinha ◽  
Salim Abdisalaam ◽  
Sunil Krishnan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Carbon Particle ◽  
Dna Lesions ◽  
X Rays ◽  
Adaptive Immune ◽  
High Let Radiation ◽  
Different Types ◽  
High Let ◽  
Radiation Induced ◽  
Tumor Death

Radiation therapy (RT), an integral component of curative treatment for many malignancies, can be administered via an increasing array of techniques. In this review, we summarize the properties and application of different types of RT, specifically, conventional therapy with x-rays, stereotactic body RT, and proton and carbon particle therapies. We highlight how low-linear energy transfer (LET) radiation induces simple DNA lesions that are efficiently repaired by cells, whereas high-LET radiation causes complex DNA lesions that are difficult to repair and that ultimately enhance cancer cell killing. Additionally, we discuss the immunogenicity of radiation-induced tumor death, elucidate the molecular mechanisms by which radiation mounts innate and adaptive immune responses and explore strategies by which we can increase the efficacy of these mechanisms. Understanding the mechanisms by which RT modulates immune signaling and the key players involved in modulating the RT-mediated immune response will help to improve therapeutic efficacy and to identify novel immunomodulatory drugs that will benefit cancer patients undergoing targeted RT.

scholarly journals Unveiling the Dynamics of KRAS4b on Lipid Model Membranes

2021 ◽  
Author(s):  
Cesar A. López ◽  
Animesh Agarwal ◽  
Que N. Van ◽  
Andrew G. Stephen ◽  
S. Gnanakaran
Keyword(s):  
Molecular Mechanisms ◽  
Hypervariable Region ◽  
Small Gtpase ◽  
Model Systems ◽  
Coarse Grained ◽  
Regulatory Function ◽  
Limited Information ◽  
Long Time ◽  
Cell Growth And Differentiation ◽  
State Models

AbstractSmall GTPase proteins are ubiquitous and responsible for regulating several processes related to cell growth and differentiation. Mutations that stabilize their active state can lead to uncontrolled cell proliferation and cancer. Although these proteins are well characterized at the cellular scale, the molecular mechanisms governing their functions are still poorly understood. In addition, there is limited information about the regulatory function of the cell membrane which supports their activity. Thus, we have studied the dynamics and conformations of the farnesylated KRAS4b in various membrane model systems, ranging from binary fluid mixtures to heterogeneous raft mimics. Our approach combines long time-scale coarse-grained (CG) simulations and Markov state models to dissect the membrane-supported dynamics of KRAS4b. Our simulations reveal that protein dynamics is mainly modulated by the presence of anionic lipids and to some extent by the nucleotide state (activation) of the protein. In addition, our results suggest that both the farnesyl and the polybasic hypervariable region (HVR) are responsible for its preferential partitioning within the liquid-disordered (Ld) domains in membranes, potentially enhancing the formation of membrane-driven signaling platforms. Graphic Abstract

scholarly journals Mangiferin as New Potential Anti-Cancer Agent and Mangiferin-Integrated Polymer Systems—A Novel Research Direction

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 79
Author(s):  
Svetlana N. Morozkina ◽  
Thi Hong Nhung Vu ◽  
Yuliya E. Generalova ◽  
Petr P. Snetkov ◽  
Mayya V. Uspenskaya
Keyword(s):  
Molecular Mechanisms ◽  
Biological Activities ◽  
Research Direction ◽  
Biological Action ◽  
The Body ◽  
Biologically Active ◽  
Polymer Systems ◽  
Anti Cancer ◽  
Long Time ◽  
Cancer Agent

For a long time, the pharmaceutical industry focused on natural biologically active molecules due to their unique properties, availability and significantly less side-effects. Mangiferin is a naturally occurring C-glucosylxantone that has substantial potential for the treatment of various diseases thanks to its numerous biological activities. Many research studies have proven that mangiferin possesses antioxidant, anti-infection, anti-cancer, anti-diabetic, cardiovascular, neuroprotective properties and it also increases immunity. It is especially important that it has no toxicity. However, mangiferin is not being currently applied to clinical use because its oral bioavailability as well as its absorption in the body are too low. To improve the solubility, enhance the biological action and bioavailability, mangiferin integrated polymer systems have been developed. In this paper, we review molecular mechanisms of anti-cancer action as well as a number of designed polymer-mangiferin systems. Taking together, mangiferin is a very promising anti-cancer molecule with excellent properties and the absence of toxicity.

scholarly journals High-Risk Human Papillomavirus and Tobacco Smoke Interactions in Epithelial Carcinogenesis

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2201 ◽  
Author(s):  
Francisco Aguayo ◽  
Juan P. Muñoz ◽  
Francisco Perez-Dominguez ◽  
Diego Carrillo-Beltrán ◽  
Carolina Oliva ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Tobacco Smoke ◽  
Molecular Mechanisms ◽  
Complex Mixture ◽  
Epidemiological Studies ◽  
Hpv Infection ◽  
Oncogenic Viruses ◽  
Cancer Initiation ◽  
Physical Environmental Factors

Cervical, anogenital, and some head and neck cancers (HNC) are etiologically associated with high-risk human papillomavirus (HR-HPV) infection, even though additional cofactors are necessary. Epidemiological studies have established that tobacco smoke (TS) is a cofactor for cervical carcinogenesis because women who smoke are more susceptible to cervical cancer when compared to non-smokers. Even though such a relationship has not been established in HPV-related HNC, a group of HPV positive patients with this malignancy are smokers. TS is a complex mixture of more than 4500 chemical compounds and approximately 60 of them show oncogenic properties such as benzo[α]pyrene (BaP) and nitrosamines, among others. Some of these compounds have been evaluated for carcinogenesis through experimental settings in collaboration with HR-HPV. Here, we conducted a comprehensive review of the suggested molecular mechanisms involved in cooperation with both HR-HPV and TS for epithelial carcinogenesis. Furthermore, we propose interaction models in which TS collaborates with HR-HPV to promote epithelial cancer initiation, promotion, and progression. More studies are warranted to clarify interactions between oncogenic viruses and chemical or physical environmental factors for epithelial carcinogenesis.

Photovoltaic Cell Test System Based on Dual-Core Processors

2011 ◽  
Vol 121-126 ◽  
pp. 4229-4233
Author(s):  
Ping Chuan Zhang ◽  
Yun Long Kong ◽  
Hang Sen Zhang
Keyword(s):  
High Performance ◽  
Fill Factor ◽  
Photovoltaic Cells ◽  
Photovoltaic Cell ◽  
Test System ◽  
Photoelectric Conversion Efficiency ◽  
Photoelectric Conversion ◽  
Data Processing Center ◽  
Cell Test ◽  
Dual Core

This paper design an intelligent photovoltaic cell test system. The high performance dual-core 16bits SPCE061A microprocessors are used as control and data processing center. The powerful data operation ability of SPCE061A makes it to carry out software filter for measured data and enhances testing precision. the experiments demonstrated the test system can measure the characteristic parameters of photovoltaic cells: open voltage, current, the fill factor and photoelectric conversion efficiency, draw photovoltaic cells I-V curve, find the best working points , and also have the characteristics of miniaturization and intelligent.

scholarly journals Genotoxicity and Gene Expression in the Rat Lung Tissue following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO2 NM)

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1502
Author(s):  
Fátima Brandão ◽  
Carla Costa ◽  
Maria João Bessa ◽  
Elise Dumortier ◽  
Florence Debacq-Chainiaux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Amorphous Silica ◽  
Oxidative Dna Damage ◽  
Intratracheal Instillation ◽  
Dna Lesions ◽  
Lung Cells ◽  
Rat Lung ◽  
Inhalation Study

Several reports on amorphous silica nanomaterial (aSiO2 NM) toxicity have been questioning their safety. Herein, we investigated the in vivo pulmonary toxicity of four variants of aSiO2 NM: SiO2_15_Unmod, SiO2_15_Amino, SiO2_7 and SiO2_40. We focused on alterations in lung DNA and protein integrity, and gene expression following single intratracheal instillation in rats. Additionally, a short-term inhalation study (STIS) was carried out for SiO2_7, using TiO2_NM105 as a benchmark NM. In the instillation study, a significant but slight increase in oxidative DNA damage in rats exposed to the highest instilled dose (0.36 mg/rat) of SiO2_15_Amino was observed in the recovery (R) group. Exposure to SiO2_7 or SiO2_40 markedly increased oxidative DNA lesions in rat lung cells of the exposure (E) group at every tested dose. This damage seems to be repaired, since no changes compared to controls were observed in the R groups. In STIS, a significant increase in DNA strand breaks of the lung cells exposed to 0.5 mg/m3 of SiO2_7 or 50 mg/m3 of TiO2_NM105 was observed in both groups. The detected gene expression changes suggest that oxidative stress and/or inflammation pathways are likely implicated in the induction of (oxidative) DNA damage. Overall, all tested aSiO2 NM were not associated with marked in vivo toxicity following instillation or STIS. The genotoxicity findings for SiO2_7 from instillation and STIS are concordant; however, changes in STIS animals were more permanent/difficult to revert.

scholarly journals Apurinic endonuclease-1 preserves neural genome integrity to maintain homeostasis and thermoregulation and prevent brain tumors

2018 ◽  
Vol 115 (52) ◽  
pp. E12285-E12294 ◽  
Author(s):  
Lavinia C. Dumitrache ◽  
Mikio Shimada ◽  
Susanna M. Downing ◽  
Young Don Kwak ◽  
Yang Li ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nervous System ◽  
Brain Tumors ◽  
Oxidative Dna Damage ◽  
Early Death ◽  
Etiologic Agent ◽  
Dna Lesions ◽  
Oxidative Modification ◽  
Early Gene ◽  
Content Type

Frequent oxidative modification of the neural genome is a by-product of the high oxygen consumption of the nervous system. Rapid correction of oxidative DNA lesions is essential, as genome stability is a paramount determinant of neural homeostasis. Apurinic/apyrimidinic endonuclease 1 (APE1; also known as “APEX1” or “REF1”) is a key enzyme for the repair of oxidative DNA damage, although the specific role(s) for this enzyme in the development and maintenance of the nervous system is largely unknown. Here, using conditional inactivation of murine Ape1, we identify critical roles for this protein in the brain selectively after birth, coinciding with tissue oxygenation shifting from a placental supply to respiration. While mice lacking APE1 throughout neurogenesis were viable with little discernible phenotype at birth, rapid and pronounced brain-wide degenerative changes associated with DNA damage were observed immediately after birth leading to early death. Unexpectedly, Ape1Nes-cre mice appeared hypothermic with persistent shivering associated with the loss of thermoregulatory serotonergic neurons. We found that APE1 is critical for the selective regulation of Fos1-induced hippocampal immediate early gene expression. Finally, loss of APE1 in combination with p53 inactivation resulted in a profound susceptibility to brain tumors, including medulloblastoma and glioblastoma, implicating oxidative DNA lesions as an etiologic agent in these diseases. Our study reveals APE1 as a major suppressor of deleterious oxidative DNA damage and uncovers specific and broad pathogenic consequences of respiratory oxygenation in the postnatal nervous system.

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