The formation of DNA adducts by genotoxic carcinogens such as polycyclic aromatic hydrocarbons (PAHs), is an essential stage in process by which these compounds cause cancer. PAHs as majority of genotoxic carcinogens require metabolic activation to form the ultimate electrophilic reactive species that covalently binds to nucleophilic sites in DNA.

Among the commonly detected environmental PAH, benzo[a]pyrene (B[a]P) is one of the most carcinogenic. Its ability to induce tumors in laboratory animals has been conclusively demonstrated. Numerous theories on the mechanism by which B[a]P is metabolically activated were proposed and ultimately discarded but one has withstood the test of time and experimentation. Two steps oxidation leads to formation of (7R, 8S)-dihydroxy-(9S,10R)epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). BPDE reacts with DNA producing a major adduct at the N2-position of deoxyguanosine (BPDE- N2-dG). Convincing evidence clearly documents the presence of this adduct in target tissues of animals treated with B[a]P. During the past 20 years, various techniques have been used to measure PAH-DNA adducts in human tissues. The most common among these are ³²P-postlabeling and immunoassay. However, none of these methods is generally selective enough to identify specific B[a]P-DNA adducts. The attempts to apply the structure-specific techniques for the analysis of human specimens surprisingly revealed that the detection of B[a]P adducts in humans is far from universal and it is not clearly related to specific exposure. The high frequency of undetectible BPDE-DNA may be explained either by not sufficient sensitivity of the methods used, low human exposure to this carcinogen or the fact that B[a]P adducts are not the appropriate analytical surrogate for carcinogenic PAH. Quantitation of adducts of the other PAH like benz[a]anthracene, fluoranthene should be considered. The progress made recently by liquid chromatography coupled to electrospray ionization mass spectrometry as a method for DNA adduct detection indicates that in future this technique will take on larger role in DNA adduct determinations in human studies. Moreover lower detection limits will be obtainable for the measurement of structurally characterized DNA adducts formed in human populations exposed to genotoxic carcinogens. Despite certain problems with detection structurally specific PAH-DNA adducts in humans measuring DNA adducts is still useful for mechanistic investigation of carcinogen activation and tumor initiation and providing clues to the etiology of human cancer.

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