Associations of cumulative occupational benzene exposure with genotoxic and immunosenescence-related biomarkers: a cross-sectional study
5 affiliations
- 1Department of Party and Mass Affairs, Shanghai Yangpu District Center for Disease Control and Prevention (Shanghai Yangpu District Health Supervision Institute)
- 2Department of Occupational Health, Hangzhou Hospital for Prevention and Treatment of Occupational Disease
- 3Shanghai Yangpu District Center for Health Promotion
- 4Department of Environmental and Occupational Health, Shanghai Yangpu District Center for Disease Control and Prevention (Shanghai Yangpu District Health Supervision Institute)
- 5Department of Physical Examination, Shanghai Institute of Occupational Disease for Chemical Industry
Abstract
Background: Chronic benzene (BZ) exposure is a well-established cause of hematological malignancies, but its potential association with immunosenescence-related alterations at occupational exposure levels below current regulatory limits remains unclear. This cross-sectional study investigated the associations of cumulative BZ exposure with genotoxicity, immunosenescence-related, and hematological biomarkers.
Methods: The study included 228 participants: 115 workers directly involved in BZ production, 75 administrative workers from the same factories without direct involvement in BZ production, and 38 external controls without occupational exposure to industrial solvents. BZ exposure was assessed using personal air monitoring, and cumulative exposure dose (CED) was calculated from airborne BZ concentrations and exposure duration. Genomic damage was evaluated using the cytokinesis-block micronucleus (CBMN) and comet assays. Immunosenescence-related and cellular-stress markers included the CD4/CD8 ratio, CD28 ⁻ frequency, p53 expression, γ -H2AX expression, and mitochondrial DNA copy number. Hematological parameters were assessed using peripheral blood cell counts. Spearman correlation analysis and outcome-appropriate generalized linear models were used to evaluate the associations between CED and the investigated biomarkers.
Results: After full multivariable adjustment, higher CED was associated with greater comet tail intensity (MR = 1.0827, p < 0.001) and tail moment (MR = 1.0922, p < 0.001) and with lower CD4/CD8 ratio (MR = 0.9743, p < 0.001) and p53 expression (MR = 0.9739, p < 0.001). CED was associated with higher micronucleus frequency (MNF) in the age- and sex-adjusted model (RR = 1.0137, p = 0.033). After further adjustment for BMI, hypertension, smoking status, and alcohol use, the effect estimate remained positive, but the association did not reach conventional statistical significance (RR = 1.0123, p = 0.053). No statistically significant associations were observed between CED and comet tail length, CD28 ⁻ frequency, γ -H2AX expression, mitochondrial DNA copy number, WBC, RBC, platelet count, or neutrophil count in the fully adjusted models.
Conclusion: Cumulative occupational BZ exposure below the applicable regulatory limits was associated with increased comet-assessed DNA damage and selected immune-related alterations, particularly lower CD4/CD8 ratio and p53 expression. The association between CED and MNF remained positive but was not statistically significant after full adjustment. These findings suggest a selective pattern of BZ-associated genotoxic and immune-related alterations rather than generalized hematological toxicity or a uniform immunosenescence phenotype. Prospective studies are needed to determine their long-term clinical and occupational health significance.
Related
- Chronic Occupational Stress and Immune–Inflammatory Dysregulation: Mechanisms, Clinical Consequences, Biomarkers and Implications for Occupational Medicine
- Associations between working hours, sleep status, and cumulative fatigue: a cross-sectional study among platform-based parcel delivery couriers in China
- Associations of sleep disturbance and emotion regulation with perceived workplace safety and fatigue among male firefighters with prior occupational accidents : A cross-sectional study
- Anemia status transitions, cumulative hemoglobin exposure, and component-specific associations with sarcopenia.
- Differential associations of baseline, dynamic change, and cumulative average TyG-BMI with incident cardiometabolic multimorbidity: a longitudinal landmark analysis of CHARLS
BibTeX
@article{xu2026associations,
title = {{Associations of cumulative occupational benzene exposure with genotoxic and immunosenescence-related biomarkers: a cross-sectional study}},
author = {Wenqian Xu and Xiaoying Ruan and Lu He and Yaying Zhang and Yun Sun},
journal = {Frontiers in Public Health},
year = {2026},
month = oct,
doi = {10.3389/fpubh.2026.1972556},
url = {https://www.frontiersin.org/articles/10.3389/fpubh.2026.1972556/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Associations of cumulative occupational benzene exposure with genotoxic and immunosenescence-related biomarkers: a cross-sectional study
AU - Wenqian Xu
AU - Xiaoying Ruan
AU - Lu He
AU - Yaying Zhang
AU - Yun Sun
PY - 2026
DA - 2026/10/14
JO - Frontiers in Public Health
DO - 10.3389/fpubh.2026.1972556
UR - https://www.frontiersin.org/articles/10.3389/fpubh.2026.1972556/full
AB - Background: Chronic benzene (BZ) exposure is a well-established cause of hematological malignancies, but its potential association with immunosenescence-related alterations at occupational exposure levels below current regulatory limits remains unclear. This cross-sectional study investigated the associations of cumulative BZ exposure with genotoxicity, immunosenescence-related, and hematological biomarkers. Methods: The study included 228 participants: 115 workers directly involved in BZ production, 75 administrative workers from the same factories without direct involvement in BZ production, and 38 external controls without occupational exposure to industrial solvents. BZ exposure was assessed using personal air monitoring, and cumulative exposure dose (CED) was calculated from airborne BZ concentrations and exposure duration. Genomic damage was evaluated using the cytokinesis-block micronucleus (CBMN) and comet assays. Immunosenescence-related and cellular-stress markers included the CD4/CD8 ratio, CD28 ⁻ frequency, p53 expression, γ -H2AX expression, and mitochondrial DNA copy number. Hematological parameters were assessed using peripheral blood cell counts. Spearman correlation analysis and outcome-appropriate generalized linear models were used to evaluate the associations between CED and the investigated biomarkers. Results: After full multivariable adjustment, higher CED was associated with greater comet tail intensity (MR = 1.0827, p < 0.001) and tail moment (MR = 1.0922, p < 0.001) and with lower CD4/CD8 ratio (MR = 0.9743, p < 0.001) and p53 expression (MR = 0.9739, p < 0.001). CED was associated with higher micronucleus frequency (MNF) in the age- and sex-adjusted model (RR = 1.0137, p = 0.033). After further adjustment for BMI, hypertension, smoking status, and alcohol use, the effect estimate remained positive, but the association did not reach conventional statistical significance (RR = 1.0123, p = 0.053). No statistically significant associations were observed between CED and comet tail length, CD28 ⁻ frequency, γ -H2AX expression, mitochondrial DNA copy number, WBC, RBC, platelet count, or neutrophil count in the fully adjusted models. Conclusion: Cumulative occupational BZ exposure below the applicable regulatory limits was associated with increased comet-assessed DNA damage and selected immune-related alterations, particularly lower CD4/CD8 ratio and p53 expression. The association between CED and MNF remained positive but was not statistically significant after full adjustment. These findings suggest a selective pattern of BZ-associated genotoxic and immune-related alterations rather than generalized hematological toxicity or a uniform immunosenescence phenotype. Prospective studies are needed to determine their long-term clinical and occupational health significance.
SN - 2296-2565
ER -