A Cross-Sectional Study on Immune-Inflammatory Responses: Exposure to Polycyclic Aromatic Hydrocarbons Alters Pteridine Metabolism and Activates the Kynurenine Pathway
Jul 2026· Chemical Research in Toxicology· Vol 39, pp. 1410 - 1417· 0 citations· 47 references
Medicine
TL;DR
Investigating the systemic biological effects of occupational exposure to PAHs from asphalt fumes in road construction workers revealed profound alterations in pteridine metabolism and activation of the kynurenine pathway, using a combined panel of exposure and mechanistic biomarkers.
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants generated from the incomplete combustion of organic materials and represent an important source of occupational and environmental exposure. Aside from their carcinogenic properties, PAHs are known to exert immunomodulatory and proinflammatory effects. Immune activation is closely associated with alterations in pteridine metabolism and activation of the kynurenine pathway; however, evidence linking PAH exposure to these immune-inflammatory pathways in humans remains limited. This study aimed to investigate the systemic biological effects of occupational exposure to PAHs from asphalt fumes in road construction workers, with a particular focus on alterations in pteridine metabolism and activation of the kynurenine pathway, using a combined panel of exposure and mechanistic biomarkers. Routine clinical parameters remained within normal ranges while urinary 1-hydroxypyrene, a well-established biomarker of internal PAH exposure, was significantly elevated, confirming substantial PAH exposure. Key findings revealed profound alterations in two critical metabolic pathways: (i) Pteridine metabolism was shifted, with increased neopterin and decreased biopterin levels, indicating activation of cell-mediated immunity and reduced cofactor availability; (ii) the kynurenine pathway was concurrently activated, as reflected by elevated kynurenine, reduced tryptophan, and increased estimated indoleamine 2,3-dioxygenase activity. These findings indicate that low-level but chronic PAH exposure induces sustained Th1-type immune activation and metabolic disturbances in the absence of overt clinical pathology, representing a state of subclinical biological adaptation.
Occupational dust is a widespread environmental contaminant associated with cardiovascular disease risk, yet its underlying molecular mechanisms remain insufficiently elucidated. This study investigated the associations between occupational respirable dust exposure (CDE) and early indicators of cardiovascular risk in 8662 participants from the China-Northern Anhui Coal Workers Cohort (C-NACWC). To explore potential mechanisms, we employed an integrative multi-omics approach, combining serum lipidomics from these participants with publicly available single-cell RNA sequencing data (GSE159677) from human atherosclerotic plaques. Higher levels of CDE were associated with an elevated cardiovascular risk score (CVRS) and adverse lipid profiles. Lipidomics analysis revealed that glycerophospholipid metabolism and insulin resistance mediated 8-21% of the associations between CDE and both CVRS and triglyceride. Single-cell RNA sequencing analysis showed that differentially expressed genes were significantly enriched in glycerophospholipid metabolism and inflammation-related pathways within the atherosclerotic microenvironment. Multi-omics integration suggested interleukin-6 (IL-6) as a potential hub gene in endothelial cells, highlighting a potential link between metabolic dysregulation and inflammatory signaling. Consistently, CDE was positively associated with serum IL-6 concentrations in these miners. Our findings suggest a potential pathway whereby occupational dust exposure is associated with increased early cardiovascular risk via glycerophospholipid metabolism and insulin resistance, which is linked to IL-6- related endothelial inflammation. These findings provide a scientific basis for integrating inflammatory biomarkers into routine occupational screenings. Furthermore, they advocate for a shift in occupational health policy toward comprehensive cardiovascular risk monitoring and personalized health management in dust-exposed populations.
Background: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental carcinogens that contribute to cancer development through oxidative stress, DNA damage, and genomic instability. However, current biomonitoring approaches often assess exposure and biological effects independently, limiting risk assessment and mechanistic interpretation. Aim: This review evaluates the complementary roles of urinary 1-hydroxypyrene glucuronide (1-OHPG) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) as integrated biomarkers linking PAH exposure with early carcinogenic events. Methods: A narrative review of published literature was conducted, focusing on PAH metabolism, the biological significance of 1-OHPG and 8-OHdG, epidemiological evidence assessing both biomarkers, sources of heterogeneity, methodological limitations, and future directions for precision environmental carcinogenesis. Results: Urinary 1-OHPG is a validated biomarker of internal PAH exposure, whereas urinary 8-OHdG reflects oxidative DNA damage induced by reactive oxygen species generated during PAH metabolism. Epidemiological studies generally demonstrate positive associations between elevated 1-OHPG and 8-OHdG in occupationally and environmentally exposed populations. Nevertheless, biological variability, mixed exposures, analytical differences, and predominantly cross-sectional study designs contribute to heterogeneity. Integrating these biomarkers provides a more comprehensive exposure–effect framework for interpreting PAH-induced carcinogenic processes. Conclusion: The combined assessment of urinary 1-OHPG and 8-OHdG strengthens biomonitoring by simultaneously evaluating internal PAH exposure and early molecular damage. This integrated framework has the potential to improve environmental cancer risk assessment and support precision environmental health. Relevance for patients: Integrated biomonitoring of urinary 1-OHPG and 8-OHdG may facilitate earlier identification of individuals at increased risk from chronic PAH exposure, enabling targeted prevention, improved surveillance, and informed public health interventions.
A. B. Awolesi· Journal of Clinical and Tran...· 0 citations
Polycyclic aromatic hydrocarbons (PAHs) are produced primarily by incomplete combustion of organic materials, including biomass burning, vehicle exhaust, and forest fires. Exposure to PAHs can induce reactive oxygen species (ROS) and oxidative stress, leading to lipid peroxidation and DNA damage. Biomass burning is a major environmental and public health problem in Chiang Mai province, containing particulate matter linked with respiratory and cardiovascular diseases. This prospective observational study aimed to evaluate the association between oxidative stress biomarkers and PAH exposure. A total of 152 participants comprised healthy controls (88), diabetes patients (35), hypertension patients (15) and diabetes + hypertension patients (14). Only participants aged more than 18 years were included. Participants who had acute respiratory infection or malignancies were excluded. This study was conducted in the pre-burning (December) and post-burning (May) periods by measuring biomarkers such as 1-OHP, MDA and 8-OHdG. Urinary 1-OHP increased significantly in the post-burning period from 0.21 ± 0.50 to 0.87 ± 1.25 μmol/mol creatinine (p < 0.001). Serum 8-OHdG increased significantly in all participants from 51.04 ± 24.90 to 66.08 ± 27.82 pg/mL (p < 0.001) and increased significantly in the diabetic and hypertension group. Serum MDA did not show any significant change post-burning (6.09 ± 3.71 to 6.00 ± 3.71 nmol/mL; p = 0.825), but MDA significantly decreased in the diabetic group (p = 0.017). 8-OHdG tended to increase in all clinical groups in the post-burning season compared to the pre-burning season, indicating oxidative DNA damage. 8-OHdG was found to be a sensitive biomarker of oxidative stress, suggesting its potential as an early indicator in haze season in vulnerable populations.
M. Ali, Xianfeng Cao, Udomsap Jaitham et al.· Toxics· 0 citations
Current evidence supports respiratory relevance of several SVOC classes but is insufficient to establish SVOCs as causal drivers of COPD progression, and future longitudinal COPD cohorts should integrate repeated environmental sampling, human biomonitoring, source attribution, mixture modeling and targeted metabolomics to clarify preventable exposure-progression pathways.
Yi Fan, Hao Zhou, Xikang Fan et al.· Ecotoxicology and Environmen...· 0 citations
Metabolic dysfunction-associated steatotic liver disease is among the most prevalent chronic liver diseases worldwide. Its increasing incidence is typically linked to over-nutrition and metabolic syndrome. However, this account remains insufficiently detailed, particularly regarding diseases in lean individuals and the generational acceleration of metabolic illnesses. The exposome encompasses the entirety of the environmental exposure throughout an individual’s life and provides a complementary framework. The liver is a pivotal organ given that it is the primary location for the biotransformation of xenobiotics. This study synthesized data suggesting that environmental chemical exposure may be a plausible and controllable factor in steatotic liver disease while distinguishing associations from causation. We reviewed the main exposure classes, including per- and polyfluoroalkyl substances, micro- and nanoplastics, endocrine-disrupting plasticizers, persistent organic pollutants, hazardous metals, and air pollution. We assessed the strength of human evidence and delineated the potential mechanisms shared by these agents, including nuclear receptor disruption, mitochondrial and oxidative injury, inflammasome activation, stellate cell fibrogenesis, gut microbiota-bile acid disruption, and developmental reprogramming, along with their documented associations with steatosis, steatohepatitis, fibrosis, and hepatocellular carcinoma. The recognition of environmental exposure redefines metabolic dysfunction-associated steatotic liver disease as chemical environment-driven. These findings have implications in risk assessment, treatment, and prevention.
A. Salman, A. Elewa, Ahmad Marwan et al.· World Journal of Translation...· 0 citations
It is emphasized that inflammation-related genes may be involved in the adverse effect of PAHs on HUA risk among coal workers and network toxicology highlighted inflammation-related genes and IL-17 pathway as possible toxicological mechanism linking PAHs exposure and HUA.
