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Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon–DNA adduct levels in human prostate
Author(s) -
John Kaarthik,
Ragavan Narasimhan,
Pratt M. Margaret,
Singh Paras B.,
AlBuheissi Salah,
Matanhelia Shyam S.,
Phillips David H.,
Poirier Miriam C.,
Martin Francis L.
Publication year - 2009
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.20898
Subject(s) - polycyclic aromatic hydrocarbon , enzyme , dna , dna adduct , gene , prostate , adduct , gene expression , chemistry , biology , microbiology and biotechnology , genetics , cancer research , biochemistry , cancer , environmental chemistry , organic chemistry
BACKGROUND Studies of migrant populations suggest that dietary and/or environmental factors play a crucial role in the etiology of prostatic adenocarcinoma (CaP). The human prostate consists of the peripheral zone (PZ), transition zone (TZ), and central zone (CZ); CaP occurs most often in the PZ. METHODS To investigate the notion that an underlying differential expression of phase I/II genes, and/or the presence of polycyclic aromatic hydrocarbon (PAH)–DNA adducts might explain the elevated PZ susceptibility, we examined prostate tissues (matched tissue sets consisting of PZ and TZ) from men undergoing radical retropubic prostatectomy for CaP (n = 26) or cystoprostatectomy (n = 1). Quantitative gene expression analysis was employed for cytochrome P450 ( CYP ) isoforms CYP1A1 , CYP1B1 , and CYP1A2 , as well as N ‐acetyltransferase 1 and 2 ( NAT1 and NAT2 ) and catechol‐ O ‐methyl transferase ( COMT ). RESULTS CYP1B1 , NAT1 , and COMT were expressed in all tissue sets; levels of CYP1B1 and NAT1 were consistently higher in the PZ compared to TZ. Immunohistochemistry confirmed the presence of CYP1B1 (nuclear‐associated and primarily in basal epithelial cells) and NAT1. Normal tissue from 23 of these aforementioned 27 matched tissue sets was analyzed for PAH–DNA adduct levels using antiserum elicited against DNA modified with r ,7 t 8‐dihydroxy‐ t ‐9,10‐oxy‐7,8,9,10‐tetrahydro‐benzo[ a ]pyrene (BPDE). PAH–DNA adduct levels were highest in glandular epithelial cells, but a comparison of PZ and TZ showed no significant differences. CONCLUSION Although expression of activating and/or detoxifying enzymes may be higher in the PZ, PAH–DNA adduct levels appear to be similar in both zones. Therefore, factors other than PAH–DNA adducts may be responsible for promotion of tumor formation in the human prostate. Prostate 69:505–519, 2009. © 2009 Wiley‐Liss, Inc.