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...
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Published in | Cancer letters Vol. 220; no. 2; pp. 145 - 154 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Ireland
Elsevier Ireland Ltd
08.04.2005
Elsevier Limited |
Subjects | |
Online Access | Get full text |
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Summary: | 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%. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0304-3835 1872-7980 |
DOI: | 10.1016/j.canlet.2004.07.036 |