scholarly journals DNA Adduct Formation of 4-Aminobiphenyl and Heterocyclic Aromatic Amines in Human Hepatocytes

2011 ◽  
Vol 24 (6) ◽  
pp. 913-925 ◽  
Author(s):  
Gwendoline Nauwelaers ◽  
Erin E. Bessette ◽  
Dan Gu ◽  
Yijin Tang ◽  
Julie Rageul ◽  
...  
Keyword(s):  
Aromatic Amines ◽  
Adduct Formation ◽  
Human Hepatocytes ◽  
Dna Adduct ◽  
Heterocyclic Aromatic Amines

Heterocyclic aromatic amines form high levels of DNA adducts in human hepatocytes

2011 ◽  
Vol 205 ◽  
pp. S38 ◽  
Author(s):  
G.C. Nauwelaers ◽  
D. Gu ◽  
V. Fessard ◽  
R. Turesky ◽  
S. Langouet
Keyword(s):  
Dna Adducts ◽  
Aromatic Amines ◽  
Human Hepatocytes ◽  
Heterocyclic Aromatic Amines

scholarly journals Constructing Xenobiotic Maps of Metabolism to Predict the Role of Enzymes in DNA Adduct Formation

2021 ◽  
Author(s):  
Maël Conan ◽  
Nathalie Théret ◽  
Sophie Langouet ◽  
Anne Siegel
Keyword(s):  
Dna Adducts ◽  
Environmental Contaminants ◽  
Food Additives ◽  
Metabolic Activation ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Heterocyclic Aromatic Amines ◽  
Reaction Prediction ◽  
Prediction Tools

Abstract Background : The liver plays a major role in the metabolic activation of xenobiotics (drugs, chemicals such as pollutants, pesticides, food additives...). Among environmental contaminants of concern, heterocyclic aromatic amines (HAA) are xenobiotics classified as possible or probable carcinogens (2A or 2B) by IARC for which low information exist in humans. While HAA is a family of more than thirty identified chemicals, the metabolism activation and DNA adduct formation have been fully characterized in human liver for few of them (MeIQx, PhIP, AalphaC). Results: We developed a modeling approach in order to predict all the possible metabolite derivatives of a xenobiotic. Our approach relies on the construction of an enriched and annotated map of derivative metabolites from an input metabolite. The pipeline assembles reaction prediction tools (SyGMa), sites of metabolism prediction tools (Way2Drug, SOMP and Fame 3), a tool to estimate the ability of a xenobotics to form DNA adducts (XenoSite Reactivity V1), and a filtering procedure based on Bayesian framework. This prediction pipeline was evaluated using caffeine and then applied to HAAs. The method was applied to determine enzyme profiles associated with the maximization of DNA adducts formation derived from each HAA. These profiles could be very different depending on the chemicals allowing to classify HAAs which have been grouped by their associated profiles. Conclusions: Overall, such a predictive toxicological model based on a in silico systems biology approach open perspectives to estimate genotoxicity of various chemical classes of environmental contaminants. Moreover, our approach based on enzymes profile determination open the perspective to predict various xenobiotics derived metabolites susceptible to bind DNA adducts in both normal and physiopathological situations.

Abstract A10: Exposure to heterocyclic aromatic amines, genetic susceptibility and bulky DNA adduct levels in blood leukocytes

2015 ◽  
Author(s):  
Vikki Ho ◽  
Sarah Peacock ◽  
Thomas E. Massey ◽  
Roger W. L. Godschalk ◽  
Frederik-Jan van Schooten ◽  
...  
Keyword(s):  
Genetic Susceptibility ◽  
Aromatic Amines ◽  
Dna Adduct ◽  
Heterocyclic Aromatic Amines ◽  
Blood Leukocytes

Ellipticine oxidation and DNA adduct formation in human hepatocytes is catalyzed by human cytochromes P450 and enhanced by cytochrome b5

Toxicology ◽  
2012 ◽  
Vol 302 (2-3) ◽  
pp. 233-241 ◽  
Author(s):  
Marie Stiborová ◽  
Jitka Poljaková ◽  
Eva Martínková ◽  
Jitka Ulrichová ◽  
Vilím Šimánek ◽  
...  
Keyword(s):  
Cytochromes P450 ◽  
Cytochrome B5 ◽  
Adduct Formation ◽  
Human Hepatocytes ◽  
Dna Adduct

scholarly journals A modeling approach to evaluate the balance between bioactivation and detoxification of MeIQx in human hepatocytes

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3703 ◽  
Author(s):  
Victorien Delannée ◽  
Sophie Langouët ◽  
Nathalie Théret ◽  
Anne Siegel
Keyword(s):  
Human Liver ◽  
Genome Instability ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Heterocyclic Aromatic Amines ◽  
Food Contaminants ◽  
Formation Pathway ◽  
Key Enzyme ◽  
Genotoxic Compounds ◽  
Organ Models

Background Heterocyclic aromatic amines (HAA) are environmental and food contaminants that are potentially carcinogenic for humans. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is one of the most abundant HAA formed in cooked meat. MeIQx is metabolized by cytochrome P450 1A2 in the human liver into detoxificated and bioactivated products. Once bioactivated, MeIQx metabolites can lead to DNA adduct formation responsible for further genome instability. Methods Using a computational approach, we developed a numerical model for MeIQx metabolism in the liver that predicts the MeIQx biotransformation into detoxification or bioactivation pathways according to the concentration of MeIQx. Results Our results demonstrate that (1) the detoxification pathway predominates, (2) the ratio between detoxification and bioactivation pathways is not linear and shows a maximum at 10 µM of MeIQx in hepatocyte cell models, and (3) CYP1A2 is a key enzyme in the system that regulates the balance between bioactivation and detoxification. Our analysis suggests that such a ratio could be considered as an indicator of MeIQx genotoxicity at a low concentration of MeIQx. Conclusions Our model permits the investigation of the balance between bioactivation (i.e., DNA adduct formation pathway through the prediction of potential genotoxic compounds) and detoxification of MeIQx in order to predict the behaviour of this environmental contaminant in the human liver. It highlights the importance of complex regulations of enzyme competitions that should be taken into account in any further multi-organ models.

Abstract 5739: Characterization of the metabolism and DNA adduct formation of 2-amino-9H-pyrido[2,3-b]indole in human hepatocytes

2012 ◽  
Author(s):  
Gwendoline C. Nauwelaërs ◽  
Yijin Tang ◽  
Dan Gu ◽  
Valérie Fessard ◽  
Robert J. Turesky ◽  
...  
Keyword(s):  
Adduct Formation ◽  
Human Hepatocytes ◽  
Dna Adduct

Gene-diet interactions in exposure to heterocyclic aromatic amines and bulky DNA adduct levels in blood leukocytes

2015 ◽  
Vol 56 (7) ◽  
pp. 609-620 ◽  
Author(s):  
Vikki Ho ◽  
Sarah Peacock ◽  
Thomas E. Massey ◽  
Roger W. L. Godschalk ◽  
Frederik J. van Schooten ◽  
...  
Keyword(s):  
Aromatic Amines ◽  
Dna Adduct ◽  
Heterocyclic Aromatic Amines ◽  
Blood Leukocytes
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