Albumin Adducts of Naphthalene Metabolites as Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons

Waidyanatha, Suramya; Zheng, Yuxin; Serdar, Berrin; Rappaport, Stephen M.

doi:10.1158/1055-9965.epi-03-0150

Cited by 37 publications

(18 citation statements)

References 37 publications

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“…This finding is consistent with a 3% reduction in naphthoquinone-albumin adduct level, and 2% reduction in 1,4-benzoquinone-albumin adduct level per year of increase in workers exposed to PAHs (Rappaport et al 2002; Waidyanatha et al 2004b). Experimental evidence also suggests that percutaneous absorption of some chemicals decrease with increasing age (Christophers & Kligman 1965; Tagami 1972; Roskos et al 1989).…”

Section: Discussionsupporting

confidence: 69%

The utility of naphthyl-keratin adducts as biomarkers for jet-fuel exposure

et al. 2011

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We investigated the association between biomarkers of dermal exposure, naphthyl-keratin adducts (NKA), and urine naphthalene biomarker levels in 105 workers routinely exposed to jet-fuel. A moderate correlation was observed between NKA and urine naphthalene levels (p = 0.061). The NKA, post-exposure breath naphthalene, and male gender were associated with an increase, while CYP2E1*6 DD and GSTT1-plus (++/+−) genotypes were associated with a decrease in urine naphthalene level (p < 0.0001). The NKA show great promise as biomarkers for dermal exposure to naphthalene. Further studies are warranted to characterize the relationship between NKA, other exposure biomarkers, and/or biomarkers of biological effects due to naphthalene and/or PAH exposure.

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Section: Discussionsupporting

confidence: 69%

The utility of naphthyl-keratin adducts as biomarkers for jet-fuel exposure

et al. 2011

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“…Hemoglobin and albumin adducts of 1,2-naphthoquinone and 1,4-naphthoquinone were also detected after administration of naphthalene to F344 rats (Waidyanatha et al, 2002(Waidyanatha et al, , 2004.…”

Section: Mass Spectrometry and Protein Adductsmentioning

confidence: 90%

“…This technique has been applied to the measurement of benzene oxide adducts to hemoglobin (Yeowell-O'Connell, McDonald, & Rappaport, 1996), of 1,2 and 1,4-benzoquinone adducts (Waidyanatha, Yeowell-O'Connel, & Rappaport, 1998) and of naphthalene oxide (Waidyanatha et al, 2002(Waidyanatha et al, , 2004.…”

Section: Mass Spectrometry and Protein Adductsmentioning

confidence: 99%

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Rubino

Pitton

Fabio

et al. 2009

Mass Spectrometry Reviews

109

170

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Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g., Calleman et al., 1978] years essentially for three purposes: (a) as passive monitors of the mean level of individual exposure to specific chemicals, either endogenously present in the human body or to which the subject is exposed through food or environmental contamination; (b) as quantitative indicators of the mean extent of the individual metabolic processing which converts a non-reactive chemical substance into its toxic products able to damage DNA (en route to cancer induction through genotoxic mechanisms) or key proteins (as in the case of several drugs, pesticides or otherwise biologically active substances); (c) to relate the extent of protein modification to that of biological function impairment (such as enzyme inhibition) finally causing the specific health damage. This review describes the role that contemporary mass spectrometry-based approaches employed in the qualitative and quantitative study of protein-electrophile adducts play in the discovery of the (bio)chemical mechanisms of toxic substances and highlights the future directions of research in this field. A particular emphasis is given to the measurement of often high levels of the protein adducts of several industrial and environmental pollutants in unexposed human populations, a phenomenon which highlights the possibility that a number of small organic molecules are generated in the human organism through minor metabolic processes, the imbalance of which may be the cause of "spontaneous" cases of cancer and of other degenerative diseases of still uncharacterized etiology. With all this in mind, it is foreseen that a holistic description of cellular functions will take advantage of new analytical methods based on time-integrated metabolomic measurements of a new biological compartment, the "adductome," aimed at better understanding integrated organism response to environmental and endogenous stressors.

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“…8B). Differences of this magnitude are consistent with results from the few studies that reported concentrations of targeted HSA-Cys 34 adducts in smokers and nonsmokers, namely, those of benzene oxide (0.113 pmol/mg HSA in nonsmokers versus 0.094 pmol/mg HSA in smokers) (35), 1,4-benzoquinone (0.687 pmol/mg HSA in nonsmokers versus 0.760 pmol/mg HSA in smokers) (36), styrene-7,8-oxide (2.54 pmol/mg HSA in nonsmokers versus 3.49 pmol/mg HSA in smokers) (37), 1,4-naphthoquinone (0.045 pmol/mg HSA in nonsmokers versus 0.061 pmol/mg HSA in smokers) (38), 1,2-naphthoquinone (0.056 pmol/mg HSA in nonsmokers versus 0.062 pmol/mg HSA in smokers (38), and the N-nitroso metabolite of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) (0.005 pmol/mg HSA in nonsmokers versus 0.005 pmol/mg HSA in smokers) (39).…”

Section: Fs-srm Of T3 Adducts From Human Samples-followingmentioning

confidence: 99%

Profiling Cys34 Adducts of Human Serum Albumin by Fixed-Step Selected Reaction Monitoring

Grigoryan

Funk

et al. 2011

Molecular & Cellular Proteomics

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A method is described for profiling putative adducts (or other unknown covalent modifications) at the Cys 34 locus of human serum albumin (HSA), which represents the preferred reaction site for small electrophilic species in human serum. By comparing profiles of putative HSACys 34 adducts across populations of interest it is theoretically possible to explore environmental causes of degenerative diseases and cancer caused by both exogenous and endogenous chemicals. We report a novel application of selected-reaction-monitoring (SRM) mass spectrometry, termed fixed-step SRM (FS-SRM), that allows detection of essentially all HSA-Cys 34 modifications over a specified range of mass increases (added masses). After tryptic digestion, HSA-Cys 34 adducts are contained in the third largest peptide (T3), which contains 21 amino acids and an average mass of 2433.87 Da. The FS-SRM method does not require that exact masses of T3 adducts be known in advance but rather uses a theoretical list of T3-adduct m/z values separated by a fixed increment of 1.5. In terms of added masses, each triply charged parent ion represents a bin of ؎2.3 Da between 9.1 Da and 351.1 Da. Synthetic T3 adducts were used to optimize FS-SRM and to establish screening rules based upon selected band y-series fragment ions. An isotopically labeled T3 adduct is added to protein digests to facilitate quantification of putative adducts. We used FS-SRM to generate putative adduct profiles from six archived specimens of HSA that had been pooled by gender, race, and smoking status. An average of 66 putative adduct hits (out of a possible 77) were detected in these samples. Putative adducts covered a wide range of concentrations, were most abundant in the mass range below 100 Da, and were more abundant in smokers than in nonsmokers. With minor modifications, the FS-SRM methodology can be applied to other nucleophilic sites and proteins. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.004606, 1-13, 2011.Reactive electrophiles, particularly aldehydes, epoxides, quinones, and short-lived oxygen and nitrogen species, have long been implicated as causes of major human diseases (1-5). These electrophiles enter the blood following metabolism of exogenous compounds, from oxidation of lipids and other natural molecules, from ionizing radiation, and from inflammation associated with infections and disease processes. Because of their short life spans in vivo, it is rarely possible to measure reactive electrophiles in body fluids. However, adducts produced by reactions with blood nucleophiles, notably hemoglobin (Hb) 1 and human serum albumin (HSA), reflect the presence of reactive electrophiles in the systemic circulation (6, 7). Levels of targeted Hb and/or HSA adducts have been investigated in human blood for several exogenous or endogenous toxicants that are either electrophilic carcinogens or their precursors, notably, acrylamide, aflatoxin B1, benzene, 1,3-butadiene, ethylene oxide, as well as assorted aromatic amines, polycyclic aromatic hydrocarbons, and aldehyde...

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Albumin Adducts of Naphthalene Metabolites as Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons

Cited by 37 publications

References 37 publications

The utility of naphthyl-keratin adducts as biomarkers for jet-fuel exposure

The utility of naphthyl-keratin adducts as biomarkers for jet-fuel exposure

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Profiling Cys34 Adducts of Human Serum Albumin by Fixed-Step Selected Reaction Monitoring

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