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IARC Monographs on the Evaluation of... 1999
Topics: Carcinogenicity Tests; Carcinogens; Humans; Hydrazines; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Salmonella typhimurium
PubMed: 10476419
DOI: No ID Found -
Environmental and Molecular Mutagenesis Aug 2022Hydrazine is a rodent carcinogen and is classified as a probable human carcinogen by IARC. Though hydrazine is positive in both in vitro and in vivo DNA strand break...
Hydrazine is a rodent carcinogen and is classified as a probable human carcinogen by IARC. Though hydrazine is positive in both in vitro and in vivo DNA strand break (comet) assays, hydrazine was reported to be negative in an in vitro mutation Muta Mouse lung epithelial cell (FE1) test, as well as in a regulatory-compliant, in vivo Big Blue mouse mutation test. In this article, mechanistic studies explored the cellular response to hydrazine. When tested in a regulatory-compliant mouse lymphoma assay, hydrazine yielded unusual, weakly positive results. This prompted an investigation into the transcriptional response to hydrazine in FE1 cells via RNA sequencing. Amongst the changes identified was a dose-dependent increase in G2/M DNA damage checkpoint activation associated genes. Flow cytometric experiments in FE1 cells revealed that hydrazine exposure led to S-phase cell cycle arrest. Clonogenic assays in a variety of cell lines harboring key DNA repair protein deficiencies indicated that hydrazine could sensitize cells lacking homology dependent repair proteins (Brca2 and Fancg). Lastly, hprt assays with hydrazine were conducted to determine whether a lack of DNA repair could lead to mutagenicity. However, no robust, dose-dependent induction of mutations was noted. The transcriptional and cell cycle response to hydrazine, coupled with functional investigations of DNA repair-deficient cell lines support the inconsistencies noted in the genetic toxicology regulatory battery. In summary, while hydrazine may be genotoxic, transcriptional and functional processes involved in cell cycle regulation and DNA repair appear to play a nuanced role in mediating the mutagenic potential.
Topics: Humans; Mice; Animals; Transcriptome; DNA Repair; DNA Damage; Mutagens; Cell Line; Carcinogens; Hydrazines
PubMed: 36176055
DOI: 10.1002/em.22508 -
Chemical Reviews Jun 2020The metallobiochemistry underlying the formation of the inorganic N-N-bond-containing molecules nitrous oxide (NO), dinitrogen (N), and hydrazine (NH) is essential to... (Review)
Review
The metallobiochemistry underlying the formation of the inorganic N-N-bond-containing molecules nitrous oxide (NO), dinitrogen (N), and hydrazine (NH) is essential to the lifestyles of diverse organisms. Similar reactions hold promise as means to use N-based fuels as alternative carbon-free energy sources. This review discusses research efforts to understand the mechanisms underlying biological N-N bond formation in primary metabolism and how the associated reactions are tied to energy transduction and organismal survival. These efforts comprise studies of both natural and engineered metalloenzymes as well as synthetic model complexes.
Topics: Hydrazines; Metalloproteins; Models, Molecular; Nitrogen; Nitrous Oxide
PubMed: 32108471
DOI: 10.1021/acs.chemrev.9b00629 -
Biosensors & Bioelectronics Jun 2017Enzyme-free electrochemical sensors enable rapid, high sensitivity measurements without the limitations associated with enzyme reporters. However, the performance of...
Enzyme-free electrochemical sensors enable rapid, high sensitivity measurements without the limitations associated with enzyme reporters. However, the performance of non-enzymatic electrochemical sensors tends to suffer from slow electrode kinetics and poor signal stability. We report a new enzyme-free electrochemical immunosensor based on a unique competitive detection scheme using methylene blue (MB), hydrazine and platinum nanoparticles (Pt NPs). This scheme is coupled with a robust immunosandwich format employing a MB-labelled detection antibody as a non-enzymatic reporter. In the presence of the target antigen, surface-immobilized MB consumes interfacial hydrazine thereby diminishing the electro-oxidation of hydrazine on Pt NPs. Thus, the concentration of the antigen is directly proportional to the reduction in the electrochemical signal. For proof-of-concept, this sensor was used to detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), an important malaria biomarker, in unadulterated human saliva samples. Chronocoulometric measurements showed that this platform exhibits pM-range sensitivity, high specificity and good reproducibility, making it well suited for many biosensing applications including noninvasive diagnostic testing.
Topics: Antibodies, Protozoan; Biosensing Techniques; Electrochemical Techniques; Humans; Hydrazines; Immunoassay; Malaria, Falciparum; Metal Nanoparticles; Methylene Blue; Models, Molecular; Plasmodium falciparum; Platinum; Proteins; Protozoan Proteins; Reproducibility of Results; Saliva
PubMed: 27829560
DOI: 10.1016/j.bios.2016.10.094 -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Antineoplastic Agents; Carcinogens; Environmental Exposure; Government Regulation; Humans; Hydrazines; Tobacco Smoke Pollution; United States
PubMed: 21852849
DOI: No ID Found -
FEMS Microbiology Reviews May 2013Anaerobic ammonium-oxidizing (anammox) bacteria primarily grow by the oxidation of ammonium coupled to nitrite reduction, using CO2 as the sole carbon source. Although... (Review)
Review
Anaerobic ammonium-oxidizing (anammox) bacteria primarily grow by the oxidation of ammonium coupled to nitrite reduction, using CO2 as the sole carbon source. Although they were neglected for a long time, anammox bacteria are encountered in an enormous species (micro)diversity in virtually any anoxic environment that contains fixed nitrogen. It has even been estimated that about 50% of all nitrogen gas released into the atmosphere is made by these 'impossible' bacteria. Anammox catabolism most likely resides in a special cell organelle, the anammoxosome, which is surrounded by highly unusual ladder-like (ladderane) lipids. Ammonium oxidation and nitrite reduction proceed in a cyclic electron flow through two intermediates, hydrazine and nitric oxide, resulting in the generation of proton-motive force for ATP synthesis. Reduction reactions associated with CO2 fixation drain electrons from this cycle, and they are replenished by the oxidation of nitrite to nitrate. Besides ammonium or nitrite, anammox bacteria use a broad range of organic and inorganic compounds as electron donors. An analysis of the metabolic opportunities even suggests alternative chemolithotrophic lifestyles that are independent of these compounds. We note that current concepts are still largely hypothetical and put forward the most intriguing questions that need experimental answers.
Topics: Adenosine Triphosphate; Bacteria, Anaerobic; Carbon Dioxide; Energy Metabolism; Environmental Microbiology; Hydrazines; Nitric Oxide; Nitrites; Oxidation-Reduction; Quaternary Ammonium Compounds
PubMed: 23210799
DOI: 10.1111/1574-6976.12014 -
Applied and Environmental Microbiology Apr 2022Ammonia-oxidizing archaea (AOA) and bacteria (AOB) perform key steps in the global nitrogen cycle, the oxidation of ammonia to nitrite. While the ammonia oxidation...
Ammonia-oxidizing archaea (AOA) and bacteria (AOB) perform key steps in the global nitrogen cycle, the oxidation of ammonia to nitrite. While the ammonia oxidation pathway is well characterized in AOB, many knowledge gaps remain about the metabolism of AOA. Hydroxylamine is an intermediate in both AOB and AOA, but homologues of hydroxylamine dehydrogenase (HAO), catalyzing bacterial hydroxylamine oxidation, are absent in AOA. Hydrazine is a substrate for bacterial HAO, while phenylhydrazine is a suicide inhibitor of HAO. Here, we examine the effect of hydrazines in AOA to gain insights into the archaeal ammonia oxidation pathway. We show that hydrazine is both a substrate and an inhibitor for AOA and that phenylhydrazine irreversibly inhibits archaeal hydroxylamine oxidation. Both hydrazine and phenylhydrazine interfered with ammonia and hydroxylamine oxidation in AOA. Furthermore, the AOA " Nitrosocosmicus franklandus" C13 oxidized hydrazine into dinitrogen (N), coupling this reaction to ATP production and O uptake. This study expands the known substrates of AOA and suggests that despite differences in enzymology, the ammonia oxidation pathways of AOB and AOA are functionally surprisingly similar. These results demonstrate that hydrazines are valuable tools for studying the archaeal ammonia oxidation pathway. Ammonia-oxidizing archaea (AOA) are among the most numerous living organisms on Earth, and they play a pivotal role in the global biogeochemical nitrogen cycle. Despite this, little is known about the physiology and metabolism of AOA. We demonstrate in this study that hydrazines are inhibitors of AOA. Furthermore, we demonstrate that the model soil AOA " Nitrosocosmicus franklandus" C13 oxidizes hydrazine to dinitrogen gas, and this reaction yields ATP. This provides an important advance in our understanding of the metabolism of AOA and expands the short list of energy-yielding compounds that AOA can use. This study also provides evidence that hydrazines can be useful tools for studying the metabolism of AOA, as they have been for the bacterial ammonia oxidizers.
Topics: Adenosine Triphosphate; Ammonia; Archaea; Bacteria; Humans; Hydrazines; Hydroxylamines; Nitrification; Phenylhydrazines; Soil Microbiology
PubMed: 35384704
DOI: 10.1128/aem.02470-21 -
Expert Opinion on Drug Metabolism &... Jan 2021The N-acetylation polymorphism has been the subject of comprehensive reviews describing the role of arylamine N-acetyltransferase 2 (NAT2) in the metabolism of numerous... (Review)
Review
INTRODUCTION
The N-acetylation polymorphism has been the subject of comprehensive reviews describing the role of arylamine N-acetyltransferase 2 (NAT2) in the metabolism of numerous aromatic amine and hydrazine drugs.
AREAS COVERED
We describe and review data that more clearly defines the effects of haplotypes and genotypes on the expression of acetylator phenotype towards selected drugs within human hepatocytes in vitro, within human hepatocyte cultures in situ, and clinical measures such as bioavailability, plasma metabolic ratios of parent to N-acetyl metabolite, elimination rate constants and plasma half-life, and/or clearance determinations in human subjects. We review several drugs (isoniazid, hydralazine, sulfamethazine, amifampridine, procainamide, sulfasalazine, amonafide and metamizole) for which phenotype-guided therapy may be important. The value of pharmacogenomics-guided isoniazid therapy for the prevention and treatment of tuberculosis is presented as a paradigm for phenotype-dependent dosing strategies.
EXPERT OPINION
Studies in human subjects and cryopreserved human hepatocytes show evidence for rapid, intermediate and slow acetylator phenotypes, with further data suggesting genetic heterogeneity within the slow acetylator phenotype. Incorporation of more robust genotype/phenotypes relationships, including genetic heterogeneity within the slow acetylator phenotype, should lead to further advancements in both health outcomes and cost benefit for prevention and treatment of tuberculosis.
Topics: Acetylation; Amines; Arylamine N-Acetyltransferase; Genotype; Hepatocytes; Humans; Hydrazines; Pharmaceutical Preparations; Pharmacogenetics; Polymorphism, Single Nucleotide
PubMed: 33094670
DOI: 10.1080/17425255.2021.1840551 -
Molecules (Basel, Switzerland) Sep 2022Based on the scaffolds widely used in drug design, a series of novel tryptophan derivatives containing 2,5-diketopiperazine and acyl hydrazine moieties have been...
Based on the scaffolds widely used in drug design, a series of novel tryptophan derivatives containing 2,5-diketopiperazine and acyl hydrazine moieties have been designed, synthesized, characterized, and evaluated for their biological activities. The bioassay results showed that the target compounds possessed moderate to good antiviral activities against tobacco mosaic virus (TMV), among which compounds , , , , and showed higher inactivation, curative, and protection activities in vivo than that of ribavirin (39 ± 1, 37 ± 1, 39 ± 1 at 500 mg/L) and comparable to that of ningnanmycin (58 ± 1, 55 ± 1, 57 ± 1% at 500 mg/L). Thus, these compounds are a promising candidate for anti-TMV development. Most of these compounds showed broad-spectrum fungicidal activities against 13 kinds of phytopathogenic fungi and selective fungicidal activities against , , and . Additionally, some of these compounds exhibited larvicidal activities against , , , , , and .
Topics: Animals; Antiviral Agents; Diketopiperazines; Drug Design; Fungicides, Industrial; Hydrazines; Insecticides; Molecular Structure; Moths; Ribavirin; Structure-Activity Relationship; Tobacco Mosaic Virus; Tryptophan
PubMed: 36144506
DOI: 10.3390/molecules27185758 -
Angewandte Chemie (International Ed. in... Jan 2021Reported here is the Pd-catalyzed C-N coupling of hydrazine with (hetero)aryl chlorides and bromides to form aryl hydrazines with catalyst loadings as low as 100 ppm...
Reported here is the Pd-catalyzed C-N coupling of hydrazine with (hetero)aryl chlorides and bromides to form aryl hydrazines with catalyst loadings as low as 100 ppm of Pd and KOH as base. Mechanistic studies revealed two catalyst resting states: an arylpalladium(II) hydroxide and arylpalladium(II) chloride. These compounds are present in two interconnected catalytic cycles and react with hydrazine and base or hydrazine alone to give the product. The selectivity of the hydroxide complex with hydrazine to form aryl over diaryl hydrazine was lower than that of the chloride complex, as well as the catalytic reaction. In contrast, the selectivity of the chloride complex closely matched that of the catalytic reaction, indicating that the aryl hydrazine is derived from this complex. Kinetic studies showed that the coupling process occurs by rate-limiting deprotonation of a hydrazine-bound arylpalladium(II) chloride complex to give an arylpalladium(II) hydrazido complex.
Topics: Catalysis; Humans; Hydrazines; Hydroxides; Molecular Structure; Palladium
PubMed: 32929852
DOI: 10.1002/anie.202011161