Mass spectrometry plays an increasingly important role in the search for and quantification of novel chemically specific biomarkers. The revolutionary advances in mass spectrometry instrumentation and technology empower scientists to specifically analyze DNA and protein adducts, considered as molecular dosimeters, derived from reactions of a carcinogen or its active metabolites with DNA or protein. Analysis of the adducted DNA bases and proteins can elucidate the chemically reactive species of carcinogens in humans and can serve as risk-associated biomarkers for early prediction of cancer risk. In this article, we review and compare the specificity, sensitivity, resolution, and ease-of-use of mass spectrometry methods developed to analyze ethylene oxide (EO)-induced DNA and protein adducts, particularly N7-(2-hydroxyethyl)guanine (N7-HEG) and N-(2-hydroxyethyl)valine (HEV), in human samples and in animal tissues. GC/ECNCI-MS analysis after HPLC cleanup is the most sensitive method for quantification of N7-HEG, but limited by the tedious sample preparation procedures. Excellent sensitivity and specificity in analysis of N7-HEG can be achieved by LC/MS/MS analysis if the mobile phase, the inlet (split or splitless), and the collision energy are properly optimized. GC/ECNCI-HRMS and GC/ECNCI-MS/MS analysis of HEV achieves the best performance as compared with GC/ECNCI-MS and GC/EI-MS. In conclusion, future improvements in high-throughput capabilities, detection sensitivity, and resolution of mass spectrometry will attract more scientists to identify and/or quantify novel molecular dosimeters or profiles of these biomarkers in toxicological and/or epidemiological studies.
Although sample size in this study was small, the repeated-measurement data provide useful reference for future studies related to biological monitoring of occupational exposure to AA.
Objective: Previous animal studies have shown that the oxytocin system might affect glucose homeostasis through the hypothalamus-pituitary-adrenal (HPA) axis and peripheral organs. Moreover, whether the effect is stratified by the polymorphism of oxytocin receptor gene (OXTR) remains unclear. Methods: In this study, we recruited 89 non-diabetic participants. Their plasma oxytocin and serum insulin profiles were obtained, and the polymorphism of OXTR rs53576 was genotyped. Results: There were significant correlations between the oxytocin level and fasting glucose level (r =-0.29, P <0.01), insulin level (r =-0.26, P = 0.01), and homeostasis model assessment-estimated insulin resistance (HOMA-IR) (r =-0.25, P = 0.01), when adjusted for age, gender, and body mass index (BMI). When further considering the stratification effects of OXTR variation, we found that the oxytocin level was significantly correlated with the fasting glucose level (r =-0.25, P = 0.04), insulin level (r =-0.35, P = 0.03), and HOMA-IR (r =-0.35, P < 0.01) in subjects with the OXTR A allele (n = 75) after adjustment for age, gender, and BMI. In addition, the oxytocin level in those with the GG genotype of OXTR was significantly negatively correlated with the leptin level (n = 14, r =-0.66, P = 0.02). Conclusion: The results demonstrated that the polymorphism of OXTR plays an important role in individual differences in the correlation of oxytocin and glucose homeostasis in nondiabetic subjects.
Acrylamide (AA), a rodent carcinogen, is widely used in industry and present in cigarette smoke as well as in foods processed at high temperatures. The metabolic activation of AA to glycidamide (GA) could be critical for AA carcinogenicity since GA causes DNA adduct formation in vivo. N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GAG), the most abundant DNA adduct of AA, is subjected to spontaneous and enzymatic depurination and excreted through urine. Urinary N7-GAG analysis can confirm AA genotoxicity and identify active species of AA metabolites in humans, thereby serving as a risk-associated biomarker for molecular epidemiology studies. This study aimed to develop an isotope-dilution solid-phase extraction liquid chromatography tandem mass spectrometry method to comparatively analyze urinary N7-GAG levels in nonsmokers and smokers. Urinary N-acetyl-S-(propionamide)-cysteine (AAMA), a metabolite of AA, was also analyzed as a biomarker for current AA exposure. Urinary N7-GAG was quantified by monitoring m/z 239 → 152 for N7-GAG and m/z 242 → 152 for (13)C3-labeled N7-GAG under positive electron spray ionization and multiple reaction mode. The median urinary N7-GAG level was 0.93 μg/g creatinine in nonsmokers (n = 33) and 1.41 μg/g creatinine in smokers (n = 30). Multiple linear regression analysis of data revealed that N7-GAG levels were only significantly associated with AAMA levels. These results demonstrate that urinary N7-GAG of nonsmokers and smokers is significantly associated with a very low level of dietary AA intake, assessed by analyzing urinary AAMA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.