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The expression of xenobiotic‐metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures
Author(s) -
AlBuheissi S.Z.,
Cole K.J.,
Hewer A.,
Kumar V.,
Bryan R.L.,
Hudson D.L.,
Patel H.R.,
Nathan S.,
Miller R.A.,
Phillips D.H.
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20400
Subject(s) - cyp1a2 , prostate , blot , carcinogen , immunohistochemistry , carcinogenesis , biology , arylamine n acetyltransferase , prostate cancer , microbiology and biotechnology , cytochrome p450 , enzyme , chemistry , cancer research , medicine , biochemistry , genetics , gene , immunology , cancer , acetylation
BACKGROUND Dietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N ‐acetyltransferase (NAT). METHODS We investigated by Western blotting and immunohistochemistry the expression of CYP1A1, CYP1A2, and NAT1 in human prostate and in prostate epithelial cells (PECs) derived from primary cultures and tested their ability to activate the dietary carcinogen 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ) and its N ‐hydroxy metabolite ( N ‐OH‐IQ) to DNA‐damaging moieties. RESULTS Western blotting identified CYP1A1, CYP1A2, and NAT1. Immunohistochemistry localized NAT1 to the cytoplasm of PECs. Inter‐individual variation was observed in the expression levels of CYP1A1, 1A2, and NAT1 (11, 75, and 35‐fold, respectively). PECs expressed CYP1A1 and NAT1 but not CYP1A2. When incubated with IQ or N ‐OH‐IQ, PECs formed DNA adducts indicating their ability to metabolically activate these compounds. CONCLUSIONS Prostate cells possess the capacity to activate dietary carcinogens. PECs may provide a useful model system to study their role in prostate carcinogenesis. Prostate © 2006 Wiley‐Liss, Inc.