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Nutrients Jun 2021Aspartame is a sweetener introduced to replace the commonly used sucrose. It was discovered by James M. Schlatter in 1965. Being 180-200 times sweeter than sucrose, its... (Review)
Review
Aspartame is a sweetener introduced to replace the commonly used sucrose. It was discovered by James M. Schlatter in 1965. Being 180-200 times sweeter than sucrose, its intake was expected to reduce obesity rates in developing countries and help those struggling with diabetes. It is mainly used as a sweetener for soft drinks, confectionery, and medicines. Despite its widespread use, its safety remains controversial. This narrative review investigates the existing literature on the use of aspartame and its possible effects on the human body to refine current knowledge. Taking to account that aspartame is a widely used artificial sweetener, it seems appropriate to continue research on safety. Studies mentioned in this article have produced very interesting results overall, the current review highlights the social problem of providing visible and detailed information about the presence of aspartame in products. The studies involving the impact of aspartame on obesity, diabetes mellitus, children and fetus, autism, neurodegeneration, phenylketonuria, allergies and skin problems, its cancer properties and its genotoxicity were analyzed. Further research should be conducted to ensure clear information about the impact of aspartame on health.
Topics: Aspartame; Food; Humans; Mental Disorders; Mutagens; Nerve Degeneration; Pharmaceutical Preparations
PubMed: 34200310
DOI: 10.3390/nu13061957 -
Science (New York, N.Y.) Oct 2022Microbiota-derived metabolites that elicit DNA damage can contribute to colorectal cancer (CRC). However, the full spectrum of genotoxic chemicals produced by indigenous...
Microbiota-derived metabolites that elicit DNA damage can contribute to colorectal cancer (CRC). However, the full spectrum of genotoxic chemicals produced by indigenous gut microbes remains to be defined. We established a pipeline to systematically evaluate the genotoxicity of an extensive collection of gut commensals from inflammatory bowel disease patients. We identified isolates from divergent phylogenies whose metabolites caused DNA damage and discovered a distinctive family of genotoxins-termed the indolimines-produced by the CRC-associated species A non-indolimine-producing mutant lacked genotoxicity and failed to exacerbate colon tumorigenesis in mice. These studies reveal the existence of a previously unexplored universe of genotoxic small molecules from the microbiome that may affect host biology in homeostasis and disease.
Topics: Animals; Mice; Colorectal Neoplasms; DNA Damage; Gastrointestinal Microbiome; Inflammatory Bowel Diseases; Morganella morganii; Indoles; Carcinogenesis; Humans; Mutagens; HeLa Cells
PubMed: 36302024
DOI: 10.1126/science.abm3233 -
International Journal of Molecular... Feb 2020During almost 40 years of use, the micronucleus assay (MN) has become one of the most popular methods to assess genotoxicity of different chemical and physical factors,... (Review)
Review
During almost 40 years of use, the micronucleus assay (MN) has become one of the most popular methods to assess genotoxicity of different chemical and physical factors, including ionizing radiation-induced DNA damage. In this minireview, we focus on the position of MN among the other genotoxicity tests, its usefulness in different applications and visibility by international organizations, such as International Atomic Energy Agency, Organization for Economic Co-operation and Development and International Organization for Standardization. In addition, the mechanism of micronuclei formation is discussed. Finally, foreseen directions of the MN development are pointed, such as automation, buccal cells MN and chromothripsis phenomenon.
Topics: DNA Damage; Forecasting; Humans; Lymphocytes; Micronuclei, Chromosome-Defective; Micronucleus Tests; Mutagenicity Tests; Mutagens; Radiation, Ionizing
PubMed: 32102335
DOI: 10.3390/ijms21041534 -
Cells Nov 2021For many years, it was thought that and played a pivotal role in autophagy, and that the knockdown of one of these genes would result in its inhibition. However, cells... (Review)
Review
For many years, it was thought that and played a pivotal role in autophagy, and that the knockdown of one of these genes would result in its inhibition. However, cells with or depletion still generate autophagic vacuoles with mainly -Golgi-originated isolation membranes and do not die. This indicates that autophagy can occur via ATG5/ATG7-independent alternative autophagy. Its molecular mechanism differs from that of the canonical pathway, including inter alia the phosphorylation of ULK1, and lack of LC3 modifications. As the alternative autophagy pathway has only recently been described, little is known of its precise role; however, a considerable body of evidence suggests that alternative autophagy participates in mitochondrion removal. This review summarizes the latest progress made in research on alternative autophagy and describes its possible molecular mechanism, roles and methods of detection, and possible modulators. There is a need for further research focused on types of autophagy, as this can elucidate the functioning of various cell types and the pathogenesis of human and animal diseases.
Topics: Animals; Autophagy; Autophagy-Related Proteins; Humans; Models, Biological; Mutagens
PubMed: 34831462
DOI: 10.3390/cells10113241 -
Chemical Research in Toxicology Jul 2023Aldehydes are widespread in the environment, with multiple sources such as food and beverages, industrial effluents, cigarette smoke, and additives. The toxic effects of... (Review)
Review
Aldehydes are widespread in the environment, with multiple sources such as food and beverages, industrial effluents, cigarette smoke, and additives. The toxic effects of exposure to several aldehydes have been observed in numerous studies. At the molecular level, aldehydes damage DNA, cross-link DNA and proteins, lead to lipid peroxidation, and are associated with increased disease risk including cancer. People genetically predisposed to aldehyde sensitivity exhibit severe health outcomes. In various diseases such as Fanconi's anemia and Cockayne syndrome, loss of aldehyde-metabolizing pathways in conjunction with defects in DNA repair leads to widespread DNA damage. Importantly, aldehyde-associated mutagenicity is being explored in a growing number of studies, which could offer key insights into how they potentially contribute to tumorigenesis. Here, we review the genotoxic effects of various aldehydes, focusing particularly on the DNA adducts underlying the mutagenicity of environmentally derived aldehydes. We summarize the chemical structures of the aldehydes and their predominant DNA adducts, discuss various methodologies, and , commonly used in measuring aldehyde-associated mutagenesis, and highlight some recent studies looking at aldehyde-associated mutation signatures and spectra. We conclude the Review with a discussion on the challenges and future perspectives of investigating aldehyde-associated mutagenesis.
Topics: Humans; Aldehydes; DNA Adducts; DNA Damage; DNA Repair; Mutagens; DNA
PubMed: 37363863
DOI: 10.1021/acs.chemrestox.3c00045 -
Toxins May 2021Colibactin is a secondary metabolite encoded by the gene island identified in several Enterobacteriaceae, including some pathogenic () commonly enriched in mucosal... (Review)
Review
Colibactin is a secondary metabolite encoded by the gene island identified in several Enterobacteriaceae, including some pathogenic () commonly enriched in mucosal tissue collected from patients with inflammatory bowel disease and colorectal cancer. harboring this biosynthetic gene cluster cause DNA damage and tumorigenesis in cell lines and pre-clinical models, yet fundamental knowledge regarding colibactin function is lacking. To accurately assess the role of in cancer etiology, the biological mechanisms governing production and delivery of colibactin by these bacteria must be elucidated. In this review, we will focus on recent advances in our understanding of colibactin's structural mode-of-action and mutagenic potential with consideration for how this activity may be regulated by physiologic conditions within the intestine.
Topics: Animals; DNA Damage; Enterobacteriaceae; Humans; Multigene Family; Mutagens; Peptides; Polyketides; Secondary Metabolism
PubMed: 34065799
DOI: 10.3390/toxins13050346 -
Virulence Dec 2022Bacterial genotoxins are peptide or protein virulence factors produced by several pathogens, which make single-strand breaks (SSBs) and/or double-strand DNA breaks... (Review)
Review
Bacterial genotoxins are peptide or protein virulence factors produced by several pathogens, which make single-strand breaks (SSBs) and/or double-strand DNA breaks (DSBs) in the target host cells. If host DNA inflictions are not resolved on time, host cell apoptosis, cell senescence, and/or even bacterial pathogen-related cancer may occur. Two multi-protein AB toxins, cytolethal distending toxin (CDT) produced by over 30 bacterial pathogens and typhoid toxin from Typhi, as well as small polyketide-peptides named colibactin that causes the DNA interstrand cross-linking and subsequent DSBs is the most well-characterized bacterial genotoxins. Using these three examples, this review discusses the mechanisms by which these toxins deliver themselves into the nucleus of the target host cells and exert their genotoxic functions at the structural and functional levels.
Topics: Bacteria; DNA Breaks, Double-Stranded; DNA Damage; Mutagens; Virulence Factors
PubMed: 35795909
DOI: 10.1080/21505594.2022.2097417 -
Marine Drugs May 2021The marine ecosystem, populated by a myriad of animals, plants, and microorganisms, is an inexhaustible reservoir of pharmacologically active molecules. Among the... (Review)
Review
The marine ecosystem, populated by a myriad of animals, plants, and microorganisms, is an inexhaustible reservoir of pharmacologically active molecules. Among the multiple secondary metabolites produced by marine sources, there are anthraquinones and their derivatives. Besides being mainly known to be produced by terrestrial species, even marine organisms and the uncountable kingdom of marine microorganisms biosynthesize anthraquinones. Anthraquinones possess many different biological activities, including a remarkable antitumor activity. However, due to their peculiar chemical structures, anthraquinones are often associated with toxicological issues, even relevant, such as genotoxicity and mutagenicity. The aim of this review is to critically describe the anticancer potential of anthraquinones derived from marine sources and their genotoxic and mutagenic potential. Marine-derived anthraquinones show a promising anticancer potential, although clinical studies are missing. Additionally, an in-depth investigation of their toxicological profile is needed before advocating anthraquinones as a therapeutic armamentarium in the oncological area.
Topics: Animals; Anthraquinones; Antineoplastic Agents; Aquatic Organisms; Cell Line, Tumor; Humans; Mutagens; Neoplasms
PubMed: 34068184
DOI: 10.3390/md19050272 -
Methods (San Diego, Calif.) Nov 2020RNA structure is critically important to RNA viruses in every part of the replication cycle. RNA structure is also utilized by DNA viruses in order to regulate gene... (Review)
Review
RNA structure is critically important to RNA viruses in every part of the replication cycle. RNA structure is also utilized by DNA viruses in order to regulate gene expression and interact with host factors. Advances in next-generation sequencing have greatly enhanced the utility of chemical probing in order to analyze RNA structure. This review will cover some recent viral RNA structural studies using chemical probing and next-generation sequencing as well as the advantages of dimethyl sulfate (DMS)-mutational profiling and sequencing (MaPseq). DMS-MaPseq is a robust assay that can easily modify RNA in vitro, in cell and in virion. A detailed protocol for whole-genome DMS-MaPseq from cells transfected with HIV-1 and the structure of TAR as determined by DMS-MaPseq is presented. DMS-MaPseq has the ability to answer a variety of integral questions about viral RNA, including how they change in different environments and when interacting with different host factors.
Topics: Genome, Viral; High-Throughput Nucleotide Sequencing; Mutagens; Mutation; Nucleic Acid Conformation; RNA Viruses; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, RNA; Sulfuric Acid Esters
PubMed: 32251733
DOI: 10.1016/j.ymeth.2020.04.001 -
Blood May 2023
Topics: Humans; Mutagens; DNA Damage; DNA-Directed DNA Polymerase; Leukemia; DNA Polymerase theta
PubMed: 37166927
DOI: 10.1182/blood.2022019509