Electrophilic compounds/metabolites present in humans, originating from endogenous processes or exogenous exposure, pose a risk to health effects through their reactions with nucleophilic sites in proteins and DNA, forming adducts. Adductomic approaches are developed to screen for adducts to biomacromolecules in vivo by mass spectrometry (MS), with the aim to detect adducts corresponding to unknown exposures from electrophiles. In the present study, adductomic screening was performed using blood samples from healthy children about 12 years old (n = 51). The frequencies of micronuclei (MN) in erythrocytes in peripheral blood were monitored as a measure of genotoxic effect/genotoxic exposure. The applied adductomic approach has been reported earlier by us and is based on analysis of N-terminal valine adducts in hemoglobin (Hb) by liquid chromatography tandem mass spectrometry (LC-MS/MS). High resolution MS was introduced for refined screening of previously unknown N-terminal Hb adducts. Measured adduct levels were compared with MN frequencies using multivariate data analysis. In the 51 individuals, a total of 24 adducts (whereof 12 were previously identified) were observed and their levels quantified. Relatively large interindividual variations in adduct levels were observed. The data analysis (with partial least-squares regression) showed that as much as 60% of the MN variation could be explained by the adduct levels. This study, for the first time, applies the combination of these sensitive methods to measure the internal dose of potentially genotoxic chemicals and genotoxic effects, respectively. The results indicate that this is a valuable approach for the characterization of exposure to chemical risk factors for the genotoxic effects present in individuals of the general population.
The general population is exposed to the genotoxic carcinogen glycidol via food containing refined edible oils where glycidol is present in the form of fatty acid esters. In this study, internal (in vivo) doses of glycidol were determined in a cohort of 50 children and in a reference group of 12 adults (non-smokers and smokers). The lifetime in vivo doses and intakes of glycidol were calculated from the levels of the hemoglobin (Hb) adduct N-(2,3-dihydroxypropyl)valine in blood samples from the subjects, demonstrating a fivefold variation between the children. The estimated mean intake (1.4 μg/kg/day) was about two times higher, compared to the estimated intake for children by the European Food Safety Authority. The data from adults indicate that the non-smoking and smoking subjects are exposed to about the same or higher levels compared to the children, respectively. The estimated lifetime cancer risk (200/105) was calculated by a multiplicative risk model from the lifetime in vivo doses of glycidol in the children, and exceeds what is considered to be an acceptable cancer risk. The results emphasize the importance to further clarify exposure to glycidol and other possible precursors that could give a contribution to the observed adduct levels.
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