Metabolic Activation of Aromatic Amine Mutagens by Simultaneous Expression of Human Cytochrome P450 1A2, NADPH-Cytochrome P450 Reductase, andN-Acetyltransferase inEscherichia coli

1998 ◽  
Vol 11 (1) ◽  
pp. 70-74 ◽  
Author(s):  
P. David Josephy ◽  
David H. Evans ◽  
Asit Parikh ◽  
F. Peter Guengerich
Keyword(s):  
Cytochrome P450 ◽  
Aromatic Amine ◽  
Metabolic Activation ◽  
Inescherichia Coli ◽  
Cytochrome P450 Reductase ◽  
Cytochrome P450 1A2 ◽  
Nadph Cytochrome ◽  
Human Cytochrome ◽  
Nadph Cytochrome P450 Reductase ◽  
Simultaneous Expression

Construction ofSalmonella typhimurium YG7108 strains, each coexpressing a form of human cytochrome P450 with NADPH-cytochrome P450 reductase

2001 ◽  
Vol 38 (4) ◽  
pp. 329-338 ◽  
Author(s):  
Ken-ichi Fujita ◽  
Kazuo Nakayama ◽  
Yoshiyuki Yamazaki ◽  
Kazuhiro Tsuruma ◽  
Masami Yamada ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Reductase ◽  
Nadph Cytochrome ◽  
P450 Reductase ◽  
Human Cytochrome ◽  
Nadph Cytochrome P450 Reductase

scholarly journals Metabolic activation of adriamycin by NADPH-cytochrome P450 reductase; overview of its biological and biochemical effects.

2002 ◽  
Vol 49 (2) ◽  
pp. 323-331 ◽  
Author(s):  
Agnieszka Bartoszek
Keyword(s):  
Cytochrome P450 ◽  
Metabolic Activation ◽  
Culture Conditions ◽  
Cytochrome P450 Reductase ◽  
Chemical Route ◽  
Nadph Cytochrome ◽  
Biochemical Effects ◽  
P450 Reductase ◽  
Multi Stage ◽  
Nadph Cytochrome P450 Reductase

NADPH-cytochrome P450 reductase (P450 reductase) is one of the enzymes implicated in the metabolism of adriamycin, a very important clinically used antitumour drug. However, apart from the enzyme involvement, so far little was known about the chemical route and biochemical effects of this process. We demonstrated that the application of P450 reductase simultaneously with adriamycin to tumour cells in culture significantly increased cytotoxicity of the drug. Under tissue culture conditions, we noticed also that, in the presence of P450 reductase, adriamycin metabolite(s), displaying an altered spectrum within the visible light range were formed. This observation was taken adavantage of to study the metabolism of adriamycin in cell-free systems, using initially the enzyme isolated from rat liver and the recently obtained recombinant human P450 reductase. The reductive conversion of the drug turned out to be a multi-stage process, which occurred only under aerobic conditions and was accompanied by excessive NADPH consumption. Further research carried out with the aid of radical scavengers and radiolabelled adriamycin revealed that the enhancement of biological activity of adriamycin by P450 reductase stemmed from the formation of alkylating metabolite(s) rather than from the promotion of redox cycling known to be induced in the presence of anthracyclines.

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