Expression of cytochrome P450 1A1 and its contribution to oxidation of a potential human carcinogen 1-phenylazo-2-naphthol (Sudan I) in human livers.
Cytochrome P450 1A1 (CYP1A1) is one of the most important enzymes implicated in the metabolic activation of carcinogens. To date, there is still conflicting evidence for the expression of enzymatically functional CYP1A1 in human liver. In the present work, we clearly demonstrate that CYP1A1 capable of metabolizing a carcinogen 1-phenylazo-2-naphthol (Sudan I) is expressed in livers of eight American Caucasian donors. Using two independent methods (immunoblotting and N-terminal sequencing), CYP1A1 protein was detected and quantified in all human hepatic microsomes tested in the study. Its levels, ranging from 0.97 to 3.0 pmol/mg protein, correlated with activities catalyzed by this enzyme [7-ethoxyresorufin O-deethylation (EROD) and oxidation of Sudan I], indicating the presence of enzymatically active CYP1A1. Even though levels of CYP1A1 expression are low, <0.7% of total hepatic CYP, the CYP1A1 contribution to oxidation of carcinogenic Sudan I in the test set of human liver microsomes ranges from 12 to 30%.
Stiborová
Marie
M
Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic. stiborov@natur.cuni.cz
Martínek
Václav
V
Rýdlová
Helena
H
Koblas
Tomás
T
Hodek
Petr
P
D002273:Carcinogens / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000503:physiopathology*; D008862:Microsomes, Liver; D009284:Naphthols / Q000378:metabolism*; D010084:Oxidation-Reduction
D002273:Carcinogens; D009284:Naphthols; C024336:1-phenylazo-2-naphthol; D019363:Cytochrome P-450 CYP1A1