The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures

S Z Al-Buheissi; K J Cole; A Hewer; V Kumar; R L Bryan; D L Hudson; H R Patel; S Nathan; R A Miller; D H Phillips

doi:10.1002/pros.20400

The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures

S Z Al-Buheissi, K J Cole, A Hewer, V Kumar, R L Bryan, D L Hudson, H R Patel, S Nathan, R A Miller, D H Phillips

Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, United Kingdom. [email protected]

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	876-885
Number of pages	10
Journal	Prostate
Volume	66
Issue number	8
DOIs	https://doi.org/10.1002/pros.20400
Publication status	Published - 1 Jun 2006

Keywords

Arylamine N-Acetyltransferase
Biotransformation
Blotting, Western
Carcinogens
Cells, Cultured
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP1A2
DNA Adducts
DNA, Neoplasm
Epithelial Cells
Gene Expression Regulation, Enzymologic
Humans
Imidazoles
Immunohistochemistry
Isoenzymes
Male
Prostate
Quinolines
Xenobiotics

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10.1002/pros.20400

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@article{e44ad8c69e284d80b824e1a7af66aee8,

title = "The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures",

abstract = "BACKGROUNDDietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT).METHODSWe 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.RESULTSWestern 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.CONCLUSIONSProstate cells possess the capacity to activate dietary carcinogens. PECs may provide a useful model system to study their role in prostate carcinogenesis.",

keywords = "Arylamine N-Acetyltransferase, Biotransformation, Blotting, Western, Carcinogens, Cells, Cultured, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1A2, DNA Adducts, DNA, Neoplasm, Epithelial Cells, Gene Expression Regulation, Enzymologic, Humans, Imidazoles, Immunohistochemistry, Isoenzymes, Male, Prostate, Quinolines, Xenobiotics",

author = "Al-Buheissi, {S Z} and Cole, {K J} and A Hewer and V Kumar and Bryan, {R L} and Hudson, {D L} and Patel, {H R} and S Nathan and Miller, {R A} and Phillips, {D H}",

year = "2006",

month = jun,

day = "1",

doi = "10.1002/pros.20400",

language = "English",

volume = "66",

pages = "876--885",

journal = "Prostate",

issn = "0270-4137",

publisher = "Wiley",

number = "8",

}

TY - JOUR

T1 - The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures

AU - Al-Buheissi, S Z

AU - Cole, K J

AU - Hewer, A

AU - Kumar, V

AU - Bryan, R L

AU - Hudson, D L

AU - Patel, H R

AU - Nathan, S

AU - Miller, R A

AU - Phillips, D H

PY - 2006/6/1

Y1 - 2006/6/1

N2 - BACKGROUNDDietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT).METHODSWe 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.RESULTSWestern 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.CONCLUSIONSProstate cells possess the capacity to activate dietary carcinogens. PECs may provide a useful model system to study their role in prostate carcinogenesis.

AB - BACKGROUNDDietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT).METHODSWe 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.RESULTSWestern 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.CONCLUSIONSProstate cells possess the capacity to activate dietary carcinogens. PECs may provide a useful model system to study their role in prostate carcinogenesis.

KW - Arylamine N-Acetyltransferase

KW - Biotransformation

KW - Blotting, Western

KW - Carcinogens

KW - Cells, Cultured

KW - Cytochrome P-450 CYP1A1

KW - Cytochrome P-450 CYP1A2

KW - DNA Adducts

KW - DNA, Neoplasm

KW - Epithelial Cells

KW - Gene Expression Regulation, Enzymologic

KW - Humans

KW - Imidazoles

KW - Immunohistochemistry

KW - Isoenzymes

KW - Male

KW - Prostate

KW - Quinolines

KW - Xenobiotics

U2 - 10.1002/pros.20400

DO - 10.1002/pros.20400

M3 - Article

C2 - 16496416

SN - 0270-4137

VL - 66

SP - 876

EP - 885

JO - Prostate

JF - Prostate

IS - 8

ER -

The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures

Abstract

Keywords

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