Albumin and hemoglobin adducts of benzo[a]pyrene in humans—Analytical methods, exposure assessment, and recommendations for future directions

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in our environment and can cause cancer. Exposure to PAHs can be assessed by protein adduct dosimetry using benzo[a]pyrene (B[a]P) as a model compound. We present an overview of analytical methods to detect B[a]P- derived protein adducts in humans, their uses in exposure assessment, and recommendations for future research. Two major methodologies, enzyme-linked immunosorbent assay (ELISA) and chemical-specific assays, could be traced in the literature but there remains limitations with both assays. ELISA is nonspecific due to cross-reactivity of the antibody with other PAHs and results are better interpreted in terms of PAH exposure. ELISA is unable to distinguish between exposed and nonexposed persons in the majority of studies. Adduct concentrations are higher by several orders of magnitude compared to those determined by chemical-specific methods. The latter methods mostly analyzed protein adducts derived by (+)-anti-B[a]P-diol epoxide. For this purpose, gas or liquid chromatography in combination with mass spectrometry or fluorescence detection were used. However, the prevalence of positive samples remained low when chemical- specific assays were used mainly due to the lack of sensitivity. Overall, data on B[a]P-derived protein adducts in humans remain inconclusive. Future research should focus on the development and standardization of a sensitive and specific method for B[a]P-derived protein adducts prior to its use in field studies. Finally, exposures of B[a]P at the workplace and via diet, a major route of exposure of the general population, can be studied. The results will contribute to the understanding of B[a]P-induced cancer and will allow for health preventive measures.

Adduct levels from benzo[a]pyrenediol epoxide: Relative formation to histidine in serum albumin and to deoxyguanosine in DNA in vitro and in vivo in mice measured by LC/MS–MS methods

“…One disadvantage with a tetrol of BPDE for monitoring doses in vivo is that this analyte does not provide any proof that it originates from a protein adduct. Kaefferlein et al concluded in their review that the protein adduct data from studies of humans exposed to BP are inconclusive and that there is a need for more sensitive and specific methods (Kaefferlein et al, 2010).…”

“…In vitro studies have shown that corresponding adducts to Hb and SA (from humans) are formed to specific carboxyl groups (by the formation of ester bonds) and to nitrogen atoms in specific residues (histidine (His)) (Brunmark et al, 1997;Day et al, 1994;Naylor et al, 1990). Chemical-specific methods such as GC/MS have been used to measure the BP tetrols released following the hydrolysis of the ester adducts to Hb or SA from exposed humans (reviewed by Kaefferlein et al, 2010). The ester adducts formed by BPDE with Hb in mice and rats may undergo hydrolysis in vivo, and are therefore, significantly less stable in vivo than the ester adducts formed with human Hb (Naylor et al, 1990), which are protected by the tertiary structure of the protein (Day et al, 1991).…”

Antibodies to Benzo[a]pyrene and Polymorphisms of Cyp1a1*2a, Cyp1a2*1f, Gstt1, and Gstm1 Genes in Healthy Men and Lung Cancer Patients

“…При этом не удавалось выявить АТ, специфичных к ад-дуктам БП-диолэпоксид-белок [20,32], хотя об-разование таких аддуктов с гемоглобином и аль-бумином у человека доказано [22,23,30,31,32]. Высокие уровни АТ к аддуктам БП-диолэпоксид-ДНК обнаружены у членов семей, в которых были больные РЛ и хронической обструктивной болез-нью легких [27].…”

“…Считается, что генетический полиморфизм ферментов биотрансформации низкомолеку-лярных ксенобиотиков CYP, GST является одним из эндогенных факторов канцерогенеза [1,2,21,28,30,37,38,41]. Аддукты метаболитов канце-рогенов с ДНК и белками, а также специфичные к ним АТ действительно обнаружены у людей, подвергающихся интенсивному канцерогенному воздействию [4,5,7,9,17,20,22,23,26,27,31,32,42,43]. А у больных злокачественными опухо-лями выявлено большее количество АТ к хими-ческим канцерогенам, чем у здоровых [3,12,39].…”

Polycyclic Aromatic Hydrocarbons a Constituent of Petroleum: Presence and Influence in the Aquatic Environment

“…It is highly likely that the same type of mechanism is operating in animals and fish. Naturally, adduct formation between PAH metabolites and human proteins and in particular human hemoglobin and serum albumin have been very well documented [170,[192][193][194][195][196][197][198][199]. However, there are a few studies concerning protein adducts in fish.…”