Chemical exposure during prenatal development has significant implications for both maternal and child health. Compared to blood, saliva is a non-invasive and less resource-intensive, alternative. Given the temporal variability of xenobiotic metabolites (XM), repeated sampling is essential. Therefore, saliva offers a valuable tool for the longitudinal assessment of prenatal exposomes. Despite its potential, no studies have explored saliva for XM measurement. This study pioneered using saliva to assess XM detectability and investigate the associations between prenatal XM and endogenous metabolomes in pregnant women. Saliva samples were analysed using mass spectrometry from 80 pregnant women at 24-34 weeks gestation. Metabolomes and exposomes were annotated using the Human Metabolome and U.S. Environmental Protection Agency databases. Metabolome-XM associations were clustered using Glay community clustering. Linear regression models, adjusted for age, estimated associations between catecholamines and XMs. XM levels were validated in a cohort of women (n = 14) with and without preeclampsia. Our study identified 582 metabolomes and 125 XM in saliva, demonstrating its potential as a matrix for exposure measurement. After false discovery rate correction, 18 109 significant metabolome-XM associations were identified. Community clustering revealed 37 connected clusters, with the largest cluster (238 nodes) enriched in tyrosine and catecholamine metabolism. Food-contact-chemicals and food-additives were significantly associated with higher catecholamine and their metabolite levels. Subgroup analyses revealed higher concentrations of these chemicals in women with preeclampsia compared to healthy controls. This study demonstrates that saliva contains valuable molecular data for measuring exposomes. Food-related chemicals were associated with higher catecholamine levels, which may be relevant to the prevalence of hypertensive crises in pregnancy.
Humans ; Female ; Pregnancy ; Saliva/metabolism* ; Pre-Eclampsia/metabolism* ; Xenobiotics/analysis* ; Adult ; Metabolome ; Maternal Health ; Mass Spectrometry

Translational medicine is an emerging idea in current medical research area. Typically, for the purpose of bridging the gap between basic and clinical research, it not only emphasizes the urgency and necessity to break the traditional working formats, including single subject centered research team and limited cooperation among different scientific groups, but also highlights a more close and frequent interaction between basic scientist and clinician. In order to reach this goal, the theory and method of systems biology should be employed. This paper mainly focused on a central issue that how to carry out an investigation on early clinical diagnosis of xenobiotic-induced intrauterine growth retardation (IUGR) by using research concept of translational medicine and method of systems biology. Briefly, a hypothesis of common mechanism of IUGR was first proposed and subsequent validation was performed via integrating--omics (e.g. genomics, proteomics, cytomics, metabonomics/metabolomics) and molecular biology techniques. Metabonomics was further utilized to explore IUGR biomarker and establish preliminary forecasting model by bioinformatics and computational biology, which is available for early diagnosis of IUGR and make a complement to current evaluation criteria.
Biomarkers ; analysis ; Computational Biology ; Early Diagnosis ; Female ; Fetal Growth Retardation ; chemically induced ; diagnosis ; metabolism ; Genomics ; Humans ; Metabolomics ; Pregnancy ; Proteomics ; Systems Biology ; Translational Medical Research ; Xenobiotics ; toxicity

Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in drug effectiveness and adverse drug reactions. The promise of a personalized medicine is beginning to be explored but requires much more clinical and translational research. Specific DNA abnormalities in some cancers already have led to effective targeted treatments. Racially determined frequency differences in pharmacogenetic traits may affect choice of treatment requiring specific testing rather than basing treatments according to racial designation. The role of genes in variable responses to foreign chemicals (xenobiotics) has been termed ecogenetics or toxicogenetics raising problems in public health and occupational medicine. Nutrigenetics refers to genetic variation in response to nutrients and may affect nutritional requirements and predisposition to chronic disease.
DNA ; analysis ; Drug-Related Side Effects and Adverse Reactions ; Ecology ; Genetic Variation ; Genome, Human ; Genotype ; Humans ; Nutritional Physiological Phenomena ; Pharmaceutical Preparations ; Pharmacogenetics ; methods ; Phenotype ; Xenobiotics

Animals ; Biomarkers, Tumor ; Drug Design ; Drug Evaluation, Preclinical ; Humans ; Magnetic Resonance Spectroscopy ; Metabolism ; genetics ; physiology ; Neoplasms ; diagnosis ; metabolism ; Pattern Recognition, Automated ; Principal Component Analysis ; Systems Biology ; Xenobiotics ; metabolism ; toxicity

PURPOSE: Cancer development depends on not only activation of oncogene or inactivation of tumor suppressor gene but also activities of enzymes involved in the metabolism of various carcinogenic xenobiotics, such as arylamine N-acetyltrasferase 2(NAT 2) and glutathione S-transferase (GSTM1). We analyzed whether genetic polymorphisms of NAT2 and GSTM1 were correlated with the mutation patterns of p53 and H-ras genes in bladder tumor tissues. MATERIALS AND METHODS: In 49 bladder cancer patients, we performed direct DNA sequencing for the detection of mutations of p53 and H-ras gene in bladder tumor tissues, and adopted PCR and PCR-RFLP techniques for the analysis of genetic polymorphisms of NAT2 and GSTM1 using patients` blood samples, respectively. RESULTS: In 18 cases, mutations in p53 were detected whereas 1 case carried two mutations; thus total of 19 mutations were detected. Sixteen of these were point mutations including 13 of transversions and 3 of transitions, and others were 1 of frameshift and 2 of microdeletions-insertions. Among 33 patients, H-ras mutations were detected in 5 cases with 2 of transitions and 3 of transversions. The frequencies of slow, intermediate, and rapid acetylator in NAT2 genotyping analysis, were 10.2%, 40.8%, and 49.0%, respectively, and GSTM1 deletions were observed in 73.5%. We could not find any significant correlations between NAT2 or GSTM1 polymorphisms and the occurence of p53(p=0.614, p=0.310) or H-ras(p=0.500, p=0.582) mutations. Also, no apparent associations were seen for specific type of p53 and H-ras mutations according to polymorphisms of NAT2(p=0.456, p=0.600) and GSTM1(p=0.378, p=0.400). CONCLUSIONS: The polymorphisms of NAT2 and GSTM1, conjugating enzymes of foreign compound metabolism, were not considered to influence occurrence and type of mutations in p53 and H-ras in human bladder cancer.
Genes, ras ; Genes, Tumor Suppressor ; Glutathione Transferase ; Humans* ; Metabolism ; Oncogenes ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Sequence Analysis, DNA ; Urinary Bladder Neoplasms* ; Urinary Bladder* ; Xenobiotics