Dataset Information

Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate.

ABSTRACT: 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 r7,t8-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.

SUBMITTER: John K

PROVIDER: S-EPMC2647988 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate.

John Kaarthik K Ragavan Narasimhan N Pratt M Margaret MM Singh Paras B PB Al-Buheissi Salah S Matanhelia Shyam S SS Phillips David H DH Poirier Miriam C MC Martin Francis L FL

The Prostate 20090401 5

<h4>Background</h4>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.<h4>Methods</h4>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 th ...[more]

PMID: 19143007

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Project description:Airborne exposures to polycyclic aromatic hydrocarbons (PAHs) are associated with adverse health outcomes. Because personal air measurements of PAHs are labor intensive and costly, spatial PAH exposure models are useful for epidemiological studies. However, few studies provide adequate spatial coverage to reflect intra-urban variability of ambient PAHs. In this study, we collected 39-40 weekly gas-phase PAH samples in southern California twice in summer and twice in winter, 2009, in order to characterize PAH source contributions and develop spatial models that can estimate gas-phase PAH concentrations at a high resolution. A spatial mixed regression model was constructed, including such variables as roadway, traffic, land-use, vegetation index, commercial cooking facilities, meteorology, and population density. Cross validation of the model resulted in an R2 of 0.66 for summer and 0.77 for winter. Results showed higher total PAH concentrations in winter. Pyrogenic sources, such as fossil fuels and diesel exhaust, were the most dominant contributors to total PAHs. PAH sources varied by season, with a higher fossil fuel and wood burning contribution in winter. Spatial autocorrelation accounted for a substantial amount of the variance in total PAH concentrations for both winter (56%) and summer (19%). In summer, other key variables explaining the variance included meteorological factors (9%), population density (15%), and roadway length (21%). In winter, the variance was also explained by traffic density (16%). In this study, source characterization confirmed the dominance of traffic and other fossil fuel sources to total measured gas-phase PAH concentrations while a spatial exposure model identified key predictors of PAH concentrations. Gas-phase PAH source characterization and exposure estimation is of high utility to epidemiologist and policy makers interested in understanding the health impacts of gas-phase PAHs and strategies to reduce emissions.

Dataset Information

Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate.

Publications

Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate.

Similar Datasets

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