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Environmental and Molecular Mutagenesis Jun 2017
Topics: Carcinogenesis; Humans; Mutagenicity Tests; Mutagens
PubMed: 28621032
DOI: 10.1002/em.22106 -
Frontiers in Bioscience (Scholar... Jan 2013Arylamines are well-known as widespread industrial and environmental mutagens and carcinogens. Their bioactivity stems from enzymatic metabolic activation to reactive... (Review)
Review
Arylamines are well-known as widespread industrial and environmental mutagens and carcinogens. Their bioactivity stems from enzymatic metabolic activation to reactive and highly electrophilic intermediates. In this work, computational investigations related to the biological activity of these compounds have been reviewed, especially focusing on studies reporting results from quantum-mechanical calculations. Correlations between relative mutagenicities and structural and electronic features of the parent amines and of their derived nitrenium ion intermediates were examined, with the aim of achieving a clearer comprehension of the main factors determining the genotoxic potential of this type of compounds.
Topics: Amines; Aniline Compounds; Carcinogens; DNA Damage; Mutagens; Quantum Theory; Structure-Activity Relationship
PubMed: 23277072
DOI: 10.2741/s393 -
Mutagenesis Nov 1988Ground chicken breast and ground beef with either endogenous or a 10-fold increase in the concentration of creatine were fried at 220 degrees C for 10 min per side. One... (Comparative Study)
Comparative Study
Ground chicken breast and ground beef with either endogenous or a 10-fold increase in the concentration of creatine were fried at 220 degrees C for 10 min per side. One patty (100 g) of chicken meat yielded 120,000 Salmonella (TA1538) revertants following metabolic activation. The pan residues had 39% of the total activity. Added creatine (10-fold the endogenous level) increased mutagen yields an average of 2-fold. Beef cooked under identical conditions yielded 150,000 revertants/100 g for the meat patties and pan residues combined. Added creatine to beef prior to cooking increased mutagen yields 3-fold. The mutagenic profiles following initial HPLC separation showed that chicken samples with endogenous or added creatine were remarkably similar. Chicken and beef HPLC mutagenicity profiles were also similar to each other, but not identical. This suggests that the general mutagen-forming reactions with the two different types of muscle are qualitatively similar with only minor quantitative differences. The pan residues from both meat types with and without added creatine showed some significant differences in the mutagen peak profile. This work suggests that the types of mutagens formed in chicken are similar to those formed in beef and that creatine appears to be involved in the formation of all the mutagenic compounds produced from fried muscle tissue.
Topics: Animals; Cattle; Chickens; Chromatography, High Pressure Liquid; Creatine; Hot Temperature; Meat; Mutagens
PubMed: 3070290
DOI: 10.1093/mutage/3.6.503 -
Food and Chemical Toxicology : An... Mar 2023Toxic plant-produced chemicals, so-called phytotoxins, constitute a category of natural compounds belonging to a diversity of chemical classes. Some of them (e.g.,...
Toxic plant-produced chemicals, so-called phytotoxins, constitute a category of natural compounds belonging to a diversity of chemical classes. Some of them (e.g., alkaloids, terpenes, saponins) are associated with high toxic potency, while for many of others no toxicological data is available. In this study, the mutagenic potential of 1586 phytotoxins, as obtained from a publicly available database, was investigated applying different in silico approaches. (Q)SAR models (including statistical-based and rule-based systems) were used for the prediction of bacterial in vitro mutagenicity (Ames test) and the results from multiple tools were combined to assign consensus predicted values (i.e., positive, negative, inconclusive). The overall consensus outcome was then employed to investigate relationships between structural features of classes of phytotoxins and potential mutagenicity, allowing the identification of structural alerts raising a specific concern. The results highlighted that about 10% of the screened compounds were predicted to have mutagenic potential and the critical classes of concern, such as alkaloids, were further investigated in terms of subclasses (e.g., indole alkaloids, isoquinoline alkaloids), getting a deeper insight into the mutagenic potential of possible naturally occurring chemicals in plant materials and their structural alerts.
Topics: Mutagens; Mutagenicity Tests; Mutagenesis; Databases, Factual; Alkaloids; Quantitative Structure-Activity Relationship
PubMed: 36563927
DOI: 10.1016/j.fct.2022.113562 -
Mutation Research Jul 19931-Ethyl-1-nitrosourea (ENU) is a potent monofunctional ethylating agent that has been found to be mutagenic in a wide variety of mutagenicity tests system from viruses... (Review)
Review
1-Ethyl-1-nitrosourea (ENU) is a potent monofunctional ethylating agent that has been found to be mutagenic in a wide variety of mutagenicity tests system from viruses to mammalian germ cells. It also has been shown to induce tumors in various organs of mammals. ENU has been used only for research purposes. ENU possesses the dual action of ethylation and carbamoylation. The ethyl group can be transferred to nucleophilic sites of cellular constituents, and the carbonyl group can be transferred to an amino group of protein. ENU is able to produce significant levels of alkylation at oxygens, such as the O6 position of guanine and the O4 position of thymine of DNA. The molecular genetic data obtained from ENU-induced mutants on various species suggest that ENU produces mainly GC-AT transitions and, to a small extent, AT-GC, AT-CG, AT-TA, GC-CG and GC-TA base substitutions. This mutation spectrum of ENU is different from that of 1-methyl-1-nitrosourea, which mainly induces GC-AT transitions. ENU is a most potent mutagen in mouse germ cells, especially in stem-cell spermatogonia. It induces intragenic mutations with high frequency in male mouse germ cells. ENU has been established as a model compound for exploring the effects of chemical mutagenesis on mouse germ cells.
Topics: Animals; DNA; Ethylnitrosourea; Humans; Male; Mice; Mutagenicity Tests; Mutagens
PubMed: 7686271
DOI: 10.1016/0165-1110(93)90005-8 -
Bioorganic & Medicinal Chemistry Sep 2011N-Nitrosodialkylamines show their mutagenicity by forming α-hydroxynitrosamines in the presence of rat S9 mix in the Ames assay. The hydroxyl radical derived from...
N-Nitrosodialkylamines show their mutagenicity by forming α-hydroxynitrosamines in the presence of rat S9 mix in the Ames assay. The hydroxyl radical derived from Fe(2+)-H(2)O(2) (Fenton's reagent) with Cu(2+) activates N-nitrosamines, with an alkyl chain longer than a propyl constituent, to a direct-acting mutagen. The reactivity of Fe(2+)-Cu(2+)-H(2)O(2) on nitrosamines in relation to their metabolic activation is not fully characterized. Here, we report the identification of the direct-acting mutagen derived from N-nitroso-N-methylpentylamine (NMPe) in the presence of Fe(2+), Cu(2+), H(2)O(2) and nitric oxide (NO), which is a product of nitrosamine metabolism. A dichloromethane extract of the NMPe reaction mixtures was fractionated by silica gel column chromatography several times and by a preparative high performance liquid chromatography (HPLC); we obtained white crystals as a product. The direct-acting mutagen that was isolated was provisionally identified as 5-ethyl-5-nitro-1-pyrazoline 1-oxide by (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and X-ray crystallography. To confirm the structure of the mutagen, the authentic compound was synthesized from 2-nitrobutene and diazomethane, followed by N-oxidation with m-chloroperoxybenzoic acid. The (1)H NMR spectral data from the direct-acting mutagen that was synthesized was identical to the data from the isolated mutagen. Furthermore, the authentic 5-ethyl-5-nitro-1-pyrazoline 1-oxide was mutagenic in Salmonella typhimurium TA1535. The results showed that 5-ethyl-5-nitro-1-pyrazoline 1-oxide was a direct-acting mutagen derived from the reaction of NMPe and Fe(2+)-Cu(2+)-H(2)O(2)-NO.
Topics: Copper; Crystallography, X-Ray; Dose-Response Relationship, Drug; Ferrous Compounds; Hydrogen Peroxide; Ions; Models, Molecular; Molecular Structure; Mutagens; Mutation; Nitric Oxide; Nitrosamines; Salmonella typhimurium; Stereoisomerism; Structure-Activity Relationship
PubMed: 21873073
DOI: 10.1016/j.bmc.2011.07.012 -
Environmental and Molecular Mutagenesis 2010Early studies on dietary mutagenesis were mostly observational, with large numbers of potential dietary mutagens being identified from every conceivable dietary source.... (Review)
Review
Early studies on dietary mutagenesis were mostly observational, with large numbers of potential dietary mutagens being identified from every conceivable dietary source. These included known dietary carcinogens such as aflatoxin B1 and benzo[a]pyrene, and hitherto unrecognized dietary mutagens, such as the pyrolysis products formed during the heating of proteinaceous materials (heterocyclic amines). The 1993 evaluation of 2-amino-3-methyl-3H-imidazo(4,5-j)quinoline as a probable human carcinogen by the International Agency for Research on Cancer was a landmark, as this was done in the absence of specific human carcinogenicity data, and strongly influenced by mutagenicity test data. In the 21st century, the field has moved from the identification of more and more mutagens, to molecular epidemiologic approaches that not only show a mutagenic effect but also seek to link it to a dietary (or environmental) cause. Effects of diet in stimulating chronic inflammation may lead to reactive species and thereby mutation as a secondary consequence, while dietary deficiencies and nutrient imbalances may be strong sources of mutagenesis. Recognition of the roles of nutrients in cell signaling processes and control of microRNAs suggest major influences on gene expression, in the absence of permanent DNA changes. Genome-wide association studies have highlighted new pathways such as JAK/STAT signaling that profoundly influence genomic instability and responses to dietary mutagens. With improved methodologies for DNA sequencing and epigenetic changes, it is time to apply more sophisticated approaches to recognizing and proving the role of diet as a primary modulator of mutagenesis in humans.
Topics: Diet; Humans; Inflammation; Molecular Epidemiology; Mutagenesis; Mutagens
PubMed: 20740647
DOI: 10.1002/em.20594 -
Environmental Science and Pollution... Sep 2022Environmental mutagens are chemical and physical substances in the environment that has a potential to induce a wide range of mutations and generate multiple... (Review)
Review
Environmental mutagens are chemical and physical substances in the environment that has a potential to induce a wide range of mutations and generate multiple physiological, biochemical, and genetic modifications in humans. Most mutagens are having genotoxic effects on the following generation through germ cells. The influence of germinal mutations on health will be determined by their frequency, nature, and the mechanisms that keep a specific mutation in the population. Early prenatal lethal mutations have less public health consequences than genetic illnesses linked with long-term medical and social difficulties. Physical and chemical mutagens are common mutagens found in the environment. These two environmental mutagens have been associated with multiple neurological disorders and carcinogenesis in humans. Thus in this study, we aim to unravel the molecular mechanism of physical mutagens (UV rays, X-rays, gamma rays), chemical mutagens (dimethyl sulfate (DMS), bisphenol A (BPA), polycyclic aromatic hydrocarbons (PAHs), 5-chlorocytosine (5ClC)), and several heavy metals (Ar, Pb, Al, Hg, Cd, Cr) implicated in DNA damage, carcinogenesis, chromosomal abnormalities, and oxidative stress which leads to multiple disorders and impacting human health. Biological tests for mutagen detection are crucial; therefore, we also discuss several approaches (Ames test and Mutatox test) to estimate mutagenic factors in the environment. The potential risks of environmental mutagens impacting humans require a deeper basic knowledge of human genetics as well as ongoing research on humans, animals, and their tissues and fluids.
Topics: Animals; Carcinogenesis; DNA Damage; Humans; Mutagenesis; Mutagenicity Tests; Mutagens; Polycyclic Aromatic Hydrocarbons
PubMed: 34410595
DOI: 10.1007/s11356-021-15442-9 -
The Journal of Toxicological Sciences Feb 1991Two in vitro tests with different genetic end points, gene mutation and chromosomal damage, and an in vivo test, preferably the micronucleus test in mice, were... (Review)
Review
Two in vitro tests with different genetic end points, gene mutation and chromosomal damage, and an in vivo test, preferably the micronucleus test in mice, were recommended as a battery system for the primary assessment of genotoxic effects of chemicals. From our comparative studies on the mutagenic potency of chemicals, it was pointed out that results should be evaluated quantitatively rather than qualitatively, since the potency varies extensively, at range of 10(7) fold, among different chemicals, and the in vitro genotoxins relatively weak tend to be negative in in vivo mutagenicity tests as well as in carcinogenicity tests in rodents. New Salmonella tester strains, called YG-series, were established, which showed a high nitroreductase or acetyltransferase activity and specifically sensitive to nitroarens or aromatic anmines in the reverse mutation assays (Ames test). These strains could detect a small amount of mutagenic aromatic amines containing in the urine of cigarette smokers. A new technique in the micronucleus test using peripheral blood erythrocytes was introduced. A cumurative genotoxic effect of benzene, for an example, was detected in the peripheral blood even several weeks after treatment every week by gavage. A cyto-flowmetric analysis can be also applied to monitoring of such effects.
Topics: Animals; Humans; Mutagenicity Tests; Mutagens
PubMed: 1920547
DOI: 10.2131/jts.16.supplementi_83 -
Environmental and Molecular Mutagenesis Jun 2017Medical devices have the potential to leach substances which, depending on the contact category of the device, can directly contact the human body. Hence, appropriate... (Review)
Review
Medical devices have the potential to leach substances which, depending on the contact category of the device, can directly contact the human body. Hence, appropriate evaluation for genetic toxicity as part of the biocompatibility risk assessment is critical. The biocompatibility risk assessment of medical devices is guided by the ISO 10993 series of standards. The recently revised ISO 10993-3 (2014) provides guidance on evaluating the genotoxicity, carcinogenicity and reproductive toxicity potential of medical devices. The revised standard includes the use of risk assessments and chemical characterization in addition to traditional genetic toxicity tests. The ISO 10993-3 standard provides guidance on the selection and preparation of test samples, and the selection of tests to evaluate genetic toxicity. Although conformance to ISO 10993-3 is required by various national regulatory agencies for specific medical device categories, there are still differences in the interpretation of the requirements within the standard which may require additional testing. Environ. Mol. Mutagen. 58:375-379, 2017. © 2017 Wiley Periodicals, Inc.
Topics: Equipment and Supplies; Mutagenicity Tests; Mutagens; Risk Assessment
PubMed: 28573657
DOI: 10.1002/em.22102