Dioxin(-like)-Related Biological Effects through Integrated Chemical-wide and Metabolome-wide Analyses.
Environ Sci Technol
; 58(1): 258-268, 2024 Jan 09.
Article
em En
| MEDLINE
| ID: mdl-38149779
ABSTRACT
Dioxin(-like) exposures are linked to adverse health effects, including cancer. However, metabolic alterations induced by these chemicals remain largely unknown. Beyond known dioxin(-like) compounds, we leveraged a chemical-wide approach to assess chlorinated co-exposures and parent compound products [termed dioxin(-like)-related compounds] among 137 occupational workers. Endogenous metabolites were profiled by untargeted metabolomics, namely, reversed-phase chromatography with negative electrospray ionization (C18-negative) and hydrophilic interaction liquid chromatography with positive electrospray ionization (HILIC-positive). We performed a metabolome-wide association study to select dioxin(-like) associated metabolic features using a 20% false discovery rate threshold. Metabolic features were then characterized by pathway enrichment analyses. There are no significant features associated with polychlorinated dibenzo-p-dioxins (PCDDs), a subgroup of known dioxin(-like) compounds. However, 3,110 C18-negative and 2,894 HILIC-positive features were associated with at least one of the PCDD-related compounds. Abundant metabolic changes were also observed for polychlorinated dibenzofuran-related and polychlorinated biphenyl-related compounds. These metabolic features were primarily enriched in pathways of amino acids, lipid and fatty acids, carbohydrates, cofactors, and nucleotides. Our study highlights the potential of chemical-wide analysis for comprehensive exposure assessment beyond targeted chemicals. Coupled with advanced endogenous metabolomics, this approach allows for an in-depth exploration of metabolic alterations induced by environmental chemicals.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bifenilos Policlorados
/
Dioxinas
/
Dibenzodioxinas Policloradas
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Environ Sci Technol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Holanda