Blood transcriptional and microRNA responses to short-term exposure to disinfection by-products in a swimming pool
Autor: | Espín-Pérez, Almudena, Font-Ribera, Laia, van Veldhoven, Karin, Krauskopf, Julian, Portengen, Lutzen, Chadeau-Hyam, Marc, Vermeulen, Roel, Grimalt, Joan O, Villanueva, Cristina M., Vineis, Paolo, Kogevinas, Manolis, Kleinjans, Jos C, de Kok, Theo M C M, One Health Chemisch, dIRAS RA-2 |
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Přispěvatelé: | One Health Chemisch, dIRAS RA-2, RS: GROW - R1 - Prevention, Toxicogenomics, RS: FSE MaCSBio, RS: FPN MaCSBio, RS: FHML MaCSBio |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
EXPRESSION
0301 basic medicine Adult Male GENES Adolescent Colorectal cancer DRINKING-WATER Physiology Gene Expression Biology Multivariate normal models Bioinformatics COLORECTAL-CANCER CELL-PROLIFERATION Transcriptome 03 medical and health sciences Young Adult 0302 clinical medicine Disinfection by-products Swimming Pools Gene expression microRNA Heart rate medicine Humans HUMAN BLADDER-CANCER Transcriptomics Gene lcsh:Environmental sciences POLYMORPHISMS General Environmental Science lcsh:GE1-350 RISK RECEPTOR 4 Bladder cancer MUTATIONS medicine.disease MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Female Body mass index Water Pollutants Chemical Disinfectants |
Zdroj: | Environment International, 110, 42-50. Elsevier Science Environment international, 110, 42. Elsevier Limited Environment International, Vol 110, Iss, Pp 42-50 (2018) |
ISSN: | 0160-4120 |
Popis: | Background: Swimming in a chlorinated pool results in high exposure levels to disinfection by-products (DBPs), which have been associated with an increased risk of bladder cancer. Objectives: By studying molecular responses at the blood transcriptome level we examined the biological processes associated with exposure to these compounds. Methods: Whole-genome gene expression and microRNA analysis was performed on blood samples collected from 43 volunteers before and 2h after 40min swimming in an indoor chlorinated pool (PISCINAII study). Exposure to THMs was measured in exhaled breath. Heart rate and kcal expenditure were measured as proxies for physical activity. Associations between exposure levels and gene expression were assessed using multivariate normal models (MVN), correcting for age, body mass index and sex. A Bonferroni threshold at 5% was applied. Results: MVN-models for the individual exposures identified 1778 genes and 23 microRNAs that were significantly associated with exposure to at least one DBP. Due to co-linearity it was not possible to statistically disentangle responses to DBP exposure from those related to physical activity. However, after eliminating previously reported transcripts associated with physical activity a large number of hits remained associated with DBP exposure. Among those, 9 were linked with bladder and 31 with colon cancer. Concordant microRNA/mRNA expressions were identified in association with DBP exposure for hsa-mir-22-3p and hsa-miR-146a-5p and their targets RCOR1 and TLR4, both related to colon cancer in association with DBP exposure. Conclusions: Short-term exposure to low levels of DBPs shows genomics responses that may be indicative of increased cancer risk. Keywords: Disinfection by-products, Transcriptomics, microRNA, Multivariate normal models |
Databáze: | OpenAIRE |
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