Abstract
Polycyclic aromatic hydrocarbons (PAHs) are combustion products of organic materials, mixtures of which contain multiple known and probable human carcinogens. PAHs occur in indoor and outdoor air, as well as in char-broiled meats and fish. Human exposure to PAHs occurs by inhalation, ingestion and topical absorption, and subsequently formed metabolites are either rendered hydrophilic and excreted, or bioactivated and bound to cellular macromolecules. The formation of PAH-DNA adducts (DNA binding products), considered a necessary step in PAH-initiated carcinogenesis, has been widely studied in experimental models and has been documented in human tissues. This review describes immunohistochemistry (IHC) studies, which reveal localization of PAH-DNA adducts in human tissues, and semi-quantify PAH-DNA adduct levels using the Automated Cellular Imaging System (ACIS). These studies have shown that PAH-DNA adducts concentrate in: basal and supra-basal epithelium of the esophagus, cervix and vulva; glandular epithelium of the prostate; and cytotrophoblast cells and syncitiotrophoblast knots of the placenta. The IHC photomicrographs reveal the ubiquitous nature of PAH-DNA adduct formation in human tissues as well as PAH-DNA adduct accumulation in specific, vulnerable, cell types. This semi-quantative method for PAH-DNA adduct measurement could potentially see widespread use in molecular epidemiology studies.
Highlights
Polycyclic aromatic hydrocarbons (PAHs) are combustion products of organic materials, mixtures of which contain multiple known and probable human carcinogens
This study shows that prostate tissue is prone to high levels of PAH-DNA damage, but suggests that additional factors contribute to prostate cancer risk
The vulva is susceptible to cancerous changes, which are less prevalent but otherwise not unlike those found in cervix. This pilot study demonstrated that PAH-DNA adducts are formed in vulvar epithelium (Table 1), but a much larger study will be required to examine the contribution of PAH-DNA damage to risk of vulvar intraepithelial neoplasia (VIN)
Summary
Human DNA adducts, as biomarkers of exposure, internal dose and biologically effective dose, are capable of initiating mutagenesis in critical genes, leading to a loss of growth control followed by tumor development [1,2,3]. Investigators recognized that in order to extend knowledge of mechanistic cancer etiology in humans it would be necessary to develop highly-sensitive, non-invasive methods of DNA adduct measurement. The resulting antiserum cross-reacted with DNA samples modified with diol-epoxides of additional PAHs including: chrysene, benzo[k]fluoranthene, dibenz[a,c]anthracene, and the bay-region and non-bay region benz[a]anthracenes [18]. These compounds are carcinogenic in animal models and have been classified by the US Environmental Protection Agency (US EPA) and the International Agency for Research on Cancer (IARC) as either known or probable human carcinogens [19]. Because human DNA likely contains adducts of multiple carcinogenic PAHs
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