Nitrite Curing of Chicken, Pork, and Beef Inhibits Oxidation but Does Not AffectN-Nitroso Compound (NOC)-Specific DNA Adduct Formation during in Vitro Digestion

2014 ◽  
Vol 62 (8) ◽  
pp. 1980-1988 ◽  
Author(s):  
Thomas Van Hecke ◽  
Julie Vanden Bussche ◽  
Lynn Vanhaecke ◽  
Els Vossen ◽  
John Van Camp ◽  
...  
Keyword(s):  
In Vitro Digestion ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Nitroso Compound

DNA adduct formation by secondary metabolites of cyclopenta[cd]pyrene in vitro

1999 ◽  
Vol 136 (2) ◽  
pp. 137-141 ◽  
Author(s):  
Ching-Hung Hsu ◽  
Paul L. Skipper ◽  
Steven R. Tannenbaum
Keyword(s):  
Secondary Metabolites ◽  
Adduct Formation ◽  
Dna Adduct

DNA adduct formation by O-phenylphenol metabolite in vivo and in vitro

1992 ◽  
Vol 13 (8) ◽  
pp. 1469-1473 ◽  
Author(s):  
Keiko Ushiyama ◽  
Fumiko Nagai ◽  
Atsuko Nakagawa ◽  
Itsu Kano
Keyword(s):  
Adduct Formation ◽  
Dna Adduct

O6-carboxymethylguanine DNA adduct formation and lipid peroxidation upon in vitro gastrointestinal digestion of haem-rich meat

2014 ◽  
Vol 58 (9) ◽  
pp. 1883-1896 ◽  
Author(s):  
Julie Vanden Bussche ◽  
Lieselot Y. Hemeryck ◽  
Thomas Van Hecke ◽  
Gunter G. C. Kuhnle ◽  
Frank Pasmans ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Gastrointestinal Digestion ◽  
In Vitro Gastrointestinal Digestion

scholarly journals Effect of 2-acetylaminofluorene and its genotoxic metabolites on DNA adduct formation and DNA damage in 3D reconstructed human skin tissue models

Mutagenesis ◽  
2019 ◽  
Author(s):  
Thomas R Downs ◽  
Volker M Arlt ◽  
Brenda C Barnett ◽  
Ryan Posgai ◽  
Stefan Pfuhler
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Human Skin ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Strong Increase ◽  
Multiple Exposures ◽  
Multiple Treatments ◽  
Reconstructed Human Skin

Abstract In vitro genotoxicity assays utilising human skin models are becoming important tools for the safety assessment of chemicals whose primary exposure is via the dermal route. In order to explore metabolic competency and inducibility of CYP450 activating enzymes, 3D reconstructed human skin tissues were topically treated with 2-acetylaminofluorene (2-AAF) and its genotoxic metabolites, N-hydroxy-2-acetylaminofluorene (N-OH-2-AAF) and N-hydroxy-2-aminofluorene (N-OH-2-AF), which primarily cause DNA damage by forming DNA adducts. 2-AAF did not increase DNA damage measured in the reconstructed skin micronucleus (RSMN) assay when administered in multiple applications at 24 h intervals but was detected in the skin comet assay in the presence of the DNA polymerase inhibitor aphidicolin (APC). Similarly, no increase was found with N-OH-2-AAF in the RSMN assay after multiple treatments whereas a single 3 h exposure to N-OH-2-AAF caused a large dose-related increase in the skin comet assay. A significant increase in the RSMN assay was only obtained with the highly reactive N-OH-2-AF metabolite after multiple treatments over 72 h, whereas N-OH-2-AF caused a strong increase after a single 3 h exposure in the skin comet assay. In support of these results, DNA adduct formation, measured by the 32P-postlabelling assay, was examined. Adduct levels after 2-AAF treatment for 3 h were minimal but increased >10-fold after multiple exposures over 48 h, suggesting that enzyme(s) that metabolise 2-AAF are induced in the skin models. As expected, a single 3 h exposure to N-OH-2-AAF and N-OH-2-AF resulted in adduct levels that were at least 10-fold greater than those after multiple exposures to 2-AAF despite ~100-fold lower tested concentrations. Our results demonstrate that DNA damage caused by 2-AAF metabolites is more efficiently detected in the skin comet assay than the RSMN assay and after multiple exposures and enzyme induction, 2-AAF-induced DNA damage can be detected in the APC-modified comet assay.

scholarly journals Deletion of cytochrome P450 oxidoreductase enhances metabolism and DNA adduct formation of benzo[a]pyrene in Hepa1c1c7 cells

Mutagenesis ◽  
2019 ◽  
Author(s):  
Lindsay Reed ◽  
Ian W H Jarvis ◽  
David H Phillips ◽  
Volker M Arlt
Keyword(s):  
Cytochrome P450 ◽  
Mouse Model ◽  
Metabolic Activation ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Environmental Carcinogen ◽  
P450 Oxidoreductase ◽  
Cyp Enzymes ◽  
Cytochrome P450 Oxidoreductase

Abstract The environmental carcinogen benzo[a]pyrene (BaP) is presumed to exert its genotoxic effects after metabolic activation by cytochrome P450 (CYP) enzymes. However, studies using the Hepatic Reductase Null (HRN) mouse model, in which cytochrome P450 oxidoreductase (POR), the electron donor to CYP enzymes, is deleted specifically in hepatocytes, have shown that loss of hepatic POR-mediated CYP function leads to greater BaP-DNA adduct formation in livers of these mice than in wild-type (WT) mice. Here, we used CRISPR/Cas9 technology to knockout (KO) POR expression in mouse hepatoma Hepa1c1c7 cells to create an in vitro model that can mimic the HRN mouse model. Western blotting confirmed the deletion of POR in POR KO Hepa1c1c7 cells whereas expression of other components of the mixed-function oxidase system including cytochrome b5 (Cyb5) and NADH:cytochrome b5 reductase (which can also serve as electron donors to CYP enzymes), and CYP1A1 was similar in BaP-exposed WT and POR KO Hepa1c1c7 cells. BaP exposure caused cytotoxicity in WT Hepa1c1c7 cells but not in POR KO Hepa1c1c7 cells. In contrast, CYP-catalysed BaP-DNA adduct levels were ~10-fold higher in POR KO Hepa1c1c7 cells than in WT Hepa1c1c7 cells, in concordance with the presence of higher levels of BaP metabolite (e.g. BaP-7,8-dihydrodiol) in the medium of cultured BaP-exposed POR KO Hepa1c1c7 cells. As was seen in the HRN mouse model, these results suggest that Cyb5 contributes to the bioactivation of BaP in POR KO Hepa1c1c7 cells. These results indicate that CYP enzymes may play a more important role in the detoxication of BaP, as opposed to its bioactivation.

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