Simultaneous quantification of eight hemoglobin adducts of genotoxic substances by isotope-dilution UHPLC-MS/MS

Gauch, Fabian; Abraham, Klaus; Monien, Bernhard H.

doi:10.1007/s00216-022-04143-y

Anal Bioanal Chem

2022

DOI: 10.1007/s00216-022-04143-y

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Simultaneous quantification of eight hemoglobin adducts of genotoxic substances by isotope-dilution UHPLC-MS/MS

Fabian Gauch

Klaus Abraham

Bernhard H. Monien

Abstract: Various genotoxic carcinogens ubiquitously present in the human environment or respective reactive metabolites form adducts in DNA and proteins, which can be used as biomarkers of internal exposure. For example, the mass spectrometric determination of Val adducts at the N-termini of hemoglobin (Hb) peptide chains after cleavage by an Edman degradation has a long tradition in occupational medicine. We developed a novel isotope-dilution UHPLC-MS/MS method for the simultaneous quantification of Val adducts of eig… Show more

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2024

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Cited by 3 publications

References 33 publications

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Internal exposure to heat-induced food contaminants in omnivores, vegans and strict raw food eaters: biomarkers of exposure to acrylamide (hemoglobin adducts, urinary mercapturic acids) and new insights on its endogenous formation

Monien,

Bergau,

Gauch

et al. 2024

Arch Toxicol

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The urinary mercapturic acids N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) are short-term biomarkers of exposure from acrylamide and its metabolite glycidamide, respectively. The medium-term exposure to acrylamide and glycidamide is monitored by the adducts N-(2-carbamoylethyl)-Val (AA-Val) and N-(2-carbamoyl-2-hydroxyethyl)-Val (GA-Val) in hemoglobin (Hb), respectively. Three questions were addressed by application of these biomarkers in two diet studies including 36 omnivores, 36 vegans and 16 strict raw food eaters (abstaining from any warmed or heated food for at least four months): first, what is the internal acrylamide exposure following a vegan or a raw food diet in comparison to that in omnivores? Second, did the exposure change between 2017 and 2021? And third, what is the stability over time of AAMA/GAMA excretion compared to that of AA-Val/GA-Val levels in Hb between both time points? Median urinary AAMA excretion per day in non-smoking omnivores, vegans and raw food eaters were 62.4, 85.4 and 15.4 µg/day, respectively; the corresponding median AA-Val levels were 27.7, 39.7 and 13.3 pmol/g Hb, respectively. Median levels in strict raw food eaters were about 25% (AAMA excretion) and 48% (AA-Val) of those in omnivores. In comparison to 2017, AAMA and GAMA excretion levels were hardly altered in 2021, however, levels of AA-Val and GA-Val in 2021 slightly increased. There was a weak correlation between AAMA excretion levels determined four years apart (rS = 0.30), and a moderate correlation between levels of AA-Val (rS = 0.55) in this timeframe. Our data in strict raw food eaters confirm a significant endogenous formation to acrylamide in a size range, which is—based on the levels of AA-Val—distinctly higher than reported previously based on levels of urinary AAMA excretion. The relatively lower AAMA excretion in raw food eaters likely represents a lower extent of glutathione conjugation due to missing hepatic first-pass metabolism in case of endogenous formation of acrylamide, which leads to a higher systemic exposure.

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Internal exposure to heat-induced food contaminants in omnivores, vegans and strict raw food eaters: biomarkers of exposure to acrylamide (hemoglobin adducts, urinary mercapturic acids) and new insights on its endogenous formation

Monien,

Bergau,

Gauch

et al. 2024

Arch Toxicol

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Internal exposure to heat-induced food contaminants in omnivores, vegans and strict raw food eaters: biomarkers of exposure to 2- and 3-monochloropropanediol (urinary excretion) and glycidol (hemoglobin adduct N-2,3-dihydroxypropyl-Val)

Monien,

Kuhlmann,

Gauch

et al. 2024

Arch Toxicol

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Fatty acid esters of 2/3-monochloropropanediol (2/3-MCPD) and glycidol are formed mainly during heat processing (deodorization) of vegetable oils, and are hydrolyzed by lipases in the gastrointestinal tract leading to the absorption of 2/3-MCPD and glycidol. The International Agency for Research on Cancer (IARC) has classified 3-MCPD as possibly and glycidol as probably carcinogenic to humans. The aims of the current work were to clarify the exposure to 2/3-MCPD and glycidol associated with different dietary habits (omnivore, vegan, raw-food eating), and the exposure development between 2017 and 2021 in German study participants. The questions were addressed using the daily urinary excretion of 2/3-MCPD and the hemoglobin adduct N-(2,3-dihydroxypropyl)-Val (DHP-Val) formed from glycidol as biomarkers of exposure, which were determined in two dietary studies including 36 omnivores, 36 vegans and 16 strict raw food eaters (abstaining from any heated food for at least four months). The median urinary excretion of 2- and 3-MCPD in non-smoking omnivores and vegans was 0.87 and 1.35 µg/day (2-MCPD), respectively, and 0.79 and 1.03 µg/day (3-MCPD), respectively. The 2/3-MCPD concentrations in urine samples of raw food eaters were usually below the limit of detection. The median DHP-Val levels in non-smoking vegans and omnivores were 3.9 pmol/g Hb each, and 1.9 pmol/g Hb in raw food eaters. Between 2017 and 2021, the exposure to 3-MCPD and glycidol did not change, however, the median 2-MCPD excretion decreased (p = 0.02, omnivores and vegans combined). The correlation between daily excretions of 2/3-MCPD determined 4 years apart was weak, whereas a moderate correlation was observed for DHP-Val (rS = 0.66) in this timeframe. In conclusion, the exposure to glycidol in omnivores and vegans was alike, whereas the 2/3-MCPD exposure was somewhat (albeit not significantly) higher in vegans. While 2/3-MCPD were hardly detectable in urine samples of raw food eaters, the median DHP-Val level (about 50% of those in omnivores) indicates a glycidol source independent of the dietary exposure.

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Identification of Specific Hemoglobin Adduct Patterns in Users of Different Tobacco/nicotine Products by Nontargeted GC–MS/MS Analysis

Pilz,

Burkhardt,

Scherer

et al. 2024

Chem. Res. Toxicol.

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Tobacco smoke contains several electrophilic constituents which are capable of forming adducts with nucleophilic sites in DNA and proteins like hemoglobin (Hb) and albumin. New nicotine and tobacco products are discussed as less harmful forms of tobacco use compared to smoking combustible cigarettes (CC) due to reduced exposure to harmful constituents. Hence, the adduct profile in users of various tobacco/ nicotine products is expected to differ characteristically. In this article, we present a novel nontargeted screening strategy using GC−MS/MS for Hb adducts based on the analysis of the respective derivatized N-terminal valine adducts after modified Edman degradation. We analyzed blood samples from a clinical study with habitual users of CCs, electronic cigarettes, heated tobacco products (HTPs), oral tobacco, nicotine replacement therapy products and nonusers of any tobacco/nicotine products. Our nontargeted approach revealed significant differences in the Hb adduct profiles of the investigated tobacco/nicotine product user groups. Adduct identification was performed by means of an internal database, retention time estimations based on the theoretical boiling points, as well as in-house synthesized reference compounds. Several chemicals that form adducts with Hb could be identified: methylating and ethylating agents, ethylene oxide, acrylonitrile, acrylamide, glycidamide and 4-hydroxybenzaldehyde. Levels were elevated in smokers compared to all other groups for Hb adducts from methylating agents, ethylene oxide, acrylonitrile, acrylamide and glycidamide. Our approach revealed higher concentrations of Hb adducts formed by ethylation, acrylamide and glycidamide in users of HTPs compared to nonusers. However, concentrations for the latter two were still lower than in smokers. Due to their long half-lives, Hb adducts related to acrylonitrile, acrylamide (glycidamide), and ethylene oxide exposure may be useful for the biochemical verification of subjectsc ompliance in longitudinal and cross-sectional studies with respect to smoking and HTP use/abstinence.

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Simultaneous quantification of eight hemoglobin adducts of genotoxic substances by isotope-dilution UHPLC-MS/MS

Cited by 3 publications

References 33 publications

Internal exposure to heat-induced food contaminants in omnivores, vegans and strict raw food eaters: biomarkers of exposure to acrylamide (hemoglobin adducts, urinary mercapturic acids) and new insights on its endogenous formation

Internal exposure to heat-induced food contaminants in omnivores, vegans and strict raw food eaters: biomarkers of exposure to acrylamide (hemoglobin adducts, urinary mercapturic acids) and new insights on its endogenous formation

Internal exposure to heat-induced food contaminants in omnivores, vegans and strict raw food eaters: biomarkers of exposure to 2- and 3-monochloropropanediol (urinary excretion) and glycidol (hemoglobin adduct N-2,3-dihydroxypropyl-Val)

Identification of Specific Hemoglobin Adduct Patterns in Users of Different Tobacco/nicotine Products by Nontargeted GC–MS/MS Analysis

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