The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures.
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.
Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, United Kingdom. salbuheissi@aol.com
S Z
SZ
Al-Buheissi
K J
KJ
Cole
A
A
Hewer
V
V
Kumar
R L
RL
Bryan
D L
DL
Hudson
H R
HR
Patel
S
S
Nathan
R A
RA
Miller
D H
DH
Phillips
D001191:Arylamine N-Acetyltransferase / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D001711:Biotransformation; D015153:Blotting, Western; D002273:Carcinogens / Q000378:metabolism; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D018736:DNA Adducts; D004273:DNA, Neoplasm / Q000032:analysis; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000166:cytology / Q000201:enzymology*; D011804:Quinolines / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism*
D002273:Carcinogens; D018736:DNA Adducts; D004273:DNA, Neoplasm; D007093:Imidazoles; D007527:Isoenzymes; D011804:Quinolines; D015262:Xenobiotics; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C032012:2-hydroxyamino-3-methylimidazolo(4,5-f)quinoline; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1