A quantitative comparison of dibenzo[a,l]pyrene-DNA adduct formation by recombinant human cytochrome P450 microsomes

1999 ◽  
Vol 26 (2) ◽  
pp. 74-82 ◽  
Author(s):  
Leon C. King ◽  
Linda Adams ◽  
Joycelyn Allison ◽  
Michael J. Kohan ◽  
Garret Nelson ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Adduct Formation ◽  
Quantitative Comparison ◽  
Dna Adduct ◽  
Human Cytochrome

Stable Expression of Human Cytochrome P450 1B1 in V79 Chinese Hamster Cells and Metabolically Catalyzed DNA Adduct Formation of Dibenzo[a,l]pyrene

1998 ◽  
Vol 11 (6) ◽  
pp. 686-695 ◽  
Author(s):  
Andreas Luch ◽  
Stephanie L. Coffing ◽  
Yong M. Tang ◽  
Anneliese Schneider ◽  
Volker Soballa ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Chinese Hamster ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Stable Expression ◽  
Chinese Hamster Cells ◽  
Cytochrome P450 1B1 ◽  
Human Cytochrome

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.

Bioactivation of Phenytoin by Human Cytochrome P450:  Characterization of the Mechanism and Targets of Covalent Adduct Formation

1997 ◽  
Vol 10 (9) ◽  
pp. 1049-1058 ◽  
Author(s):  
Andrew J. Munns ◽  
James J. De Voss ◽  
Wayne D. Hooper ◽  
Ronald G. Dickinson ◽  
Elizabeth M. J. Gillam
Keyword(s):  
Cytochrome P450 ◽  
Adduct Formation ◽  
Human Cytochrome ◽  
Covalent Adduct
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