Modified Ames test using a strain expressing human sulfotransferase 1C2 to assess the mutagenicity of methyleugenol

Honda, Hiroshi; Minegawa, Kazuyuki; Fujita, Yuzo; Yamaguchi, Noriko; Oguma, Yoshihiro; Glatt, Hansruedi; Nishiyama, Naohiro; Kasamatsu, Toshio

doi:10.1186/s41021-016-0028-x

Cited by 29 publications

(22 citation statements)

References 20 publications

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“…In addition, XRCC1 does not appear to influence cisplatin ICL non-productive processing. The pathways on the right side are productive ICL DNA repair pathways that have been shown to occur in both G0/G1 and S phases of the cell cycle [reviewed in (45, 46)]. We have previously shown an epistatic relationship between BER and MMR in mediating cisplatin sensitivity via specific nucleotide mis-incorporation by Polβ at cisplatin ICL sites and subsequent MMR protein binding (12).…”

Section: Figurementioning

confidence: 99%

Differential role of base excision repair proteins in mediating cisplatin cytotoxicity

et al. 2017

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Interstrand crosslinks (ICLs) are covalent lesions formed by cisplatin. The mechanism for the processing and removal of ICLs by DNA repair proteins involves nucleotide excision repair (NER), homologous recombination (HR) and fanconi anemia (FA) pathways. In this report, we monitored the processing of a flanking uracil adjacent to a cisplatin ICL by the proteins involved in the base excision repair (BER) pathway. Using a combination of extracts, purified proteins, inhibitors, functional assays and cell culture studies, we determined the specific BER proteins required for processing a DNA substrate with a uracil adjacent to a cisplatin ICL. Uracil DNA glycosylase (UNG) is the primary glycosylase responsible for the removal of uracils adjacent to cisplatin ICLs, whereas other uracil glycosylases can process uracils in the context of undamaged DNA. Repair of the uracil adjacent to cisplatin ICLs proceeds through the classical BER pathway, highlighting the importance of specific proteins in this redundant pathway. Removal of uracil is followed by the generation of an abasic site and subsequent cleavage by AP endonuclease 1 (APE1). Inhibition of either the repair or redox domain of APE1 gives rise to cisplatin resistance. Inhibition of the lyase domain of Polymerase β (Polβ) does not influence cisplatin cytotoxicity. In addition, lack of XRCC1 leads to increased DNA damage and results in increased cisplatin cytotoxicity. Our results indicate that BER activation at cisplatin ICLs influences crosslink repair and modulates cisplatin cytotoxicity via specific UNG, APE1 and Polβ polymerase functions.

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Section: Figurementioning

confidence: 99%

Differential role of base excision repair proteins in mediating cisplatin cytotoxicity

et al. 2017

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“…Treatment of rats with Aroclor-1254 preferentially induces oxidative liver enzymes, particularly cytochrome P450 families 1-3 (Dubois et al 1996) and favors oxidative activation. However, the conjugating activity of such S9 mix is limited, especially in the absence of added cofactors (Glatt et al 2012;Honda et al 2016), and thus this model does not totally represent the mammalian biotransformation capabilities. Furthermore, the cytochrome P450 (P450) enzymes induced in rat liver are not fully representative of the P450 activity profile of human liver (Dubois et al 1996).…”

Section: Metabolic Activationmentioning

confidence: 99%

“…Among the key human enzymes poorly represented in rat liver S9 are sulfotransferase (SULT), N-acetyl transferase (NAT), and some extrahepatic P450 enzymes such as CYP1B1 (Jin et al 2018). Therefore, the metabolite profile can be substantially different in genotoxicity models compared to the human metabolite profile and may lead to either false positive or false negative results depending on whether the biotransformation is skewed toward the generation of reactive intermediates or detoxication products of the primary compounds (Glatt et al 2012;Honda et al 2016).…”

Section: Metabolic Activationmentioning

confidence: 99%

The safety evaluation of food flavoring substances: the role of genotoxicity studies

Gooderham

Cohen

Eisenbrand

et al. 2020

Critical Reviews in Toxicology

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The Flavor and Extract Manufacturers Association (FEMA) Expert Panel relies on the weight of evidence from all available data in the safety evaluation of flavoring substances. This process includes data from genotoxicity studies designed to assess the potential of a chemical agent to react with DNA or otherwise cause changes to DNA, either in vitro or in vivo. The Panel has reviewed a large number of in vitro and in vivo genotoxicity studies during the course of its ongoing safety evaluations of flavorings. The adherence of genotoxicity studies to standardized protocols and guidelines, the biological relevance of the results from those studies, and the human relevance of these studies are all important considerations in assessing whether the results raise specific concerns for genotoxic potential. The Panel evaluates genotoxicity studies not only for evidence of genotoxicity hazard, but also for the probability of risk to the consumer in the context of exposure from their use as flavoring substances. The majority of flavoring substances have given no indication of genotoxic potential in studies evaluated by the FEMA Expert Panel. Examples illustrating the assessment of genotoxicity data for flavoring substances and the consideration of the factors noted above are provided. The weight of evidence approach adopted by the FEMA Expert Panel leads to a rational assessment of risk associated with consumer intake of flavoring substances under the conditions of use.

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“…Antibacterial action of the combined mixes was tried against five bacterial strains and three parasitic strains utilizing agar well dispersion technique [15][16][17][18]. Dimethyl sulfoxide was utilized as dissolvable control.…”

Section: Antimicrobial Activitymentioning

confidence: 99%

In silico toxicity prediction, synthesis, characterization, antimicrobial and antioxidant activity of different di substituted chalcones

2020

Lett Appl NanoBioSci

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Right now the amalgamation of novel arrangement of 4'- chloro-3'- nitro-phenyl-(3-keto-1,2diene-1-flurobenzene), 4'- chloro-3'nitro-phenyl-(3-keto-1,2diene-1-chlorobenzene),4'- chloro-3'- nitro-phenyl-(3-keto-1,2diene-1-thiophene),4'- chloro-3'nitro-phenyl-(3-keto-1,2diene-1-pyridine), 4'- chloro-3'nitro-phenyl-(3-keto-1,2diene-1-furon).The target mixes were integrated by the Claisen-schimidt buildup utilizing corrosive and base as a response impetus. insilico enhancement strategies by utilization of various information base like molinspiration for atomic properties, bioactivity, ochem for organic information, pre ADME for pharmacokinetic properties, preToxicity for harmfulness profile of the mixes, swiss ADME for pharmacokinetic property, Swiss lethality for natural danger of the mixes, and Osiris(datawarrior) for poisonous quality forecast for dynamic lead particles ID. From the outcome mixes indented as dynamic leads they used to assess distinctive organic action. The mixes additionally finish the amees assessment for the most part for mutagenecity discovery that mixes shows mutagencity towards the test living being they likewise safe to hinder cytochrome P450 compound subunits like cyp1A2, cyp2C9, cyp2C19 which are situated in endoplasmic reticulum. Alpha beta unsaturated chalcones have fantastic cell reinforcement and antimicrobial action so the orchestrated mixes were screened for their antimicrobial by utilizing five bacterial strains and three parasitic strains and cancer prevention agent action by DPPH technique. From hostile to oxidant results compound 3a, 3b, 3c show critical action the measure esteems are closer to standard medication esteem. Antimicrobial movement results the compound 3a, 3c, 3e indicated noteworthy action against Bacillus subtilis, E Coli, Salmonella tyhphi, Pseudomonas aeruginosa though the compound 3b, 3d demonstrated moderate activitycompared to standard medication vale. Compound 3b, 3d demonstrated fantastic antifungal action against Candida albicans, Aspergillusniger, Alternariaalternata. The mixes 3a, 3c, 3e show moderate antifungal movement when contrasted with standard worth.

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Modified Ames test using a strain expressing human sulfotransferase 1C2 to assess the mutagenicity of methyleugenol

Cited by 29 publications

References 20 publications

Differential role of base excision repair proteins in mediating cisplatin cytotoxicity

Differential role of base excision repair proteins in mediating cisplatin cytotoxicity

The safety evaluation of food flavoring substances: the role of genotoxicity studies

In silico toxicity prediction, synthesis, characterization, antimicrobial and antioxidant activity of different di substituted chalcones

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