Benzene and cigarette smoke co-exposure exacerbates hematotoxicity involving the AhR–NLRP3 signaling pathway
- 1Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong, 250062, China
- 2Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong, 250062, China; Corresponding authors.
- 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China; Corresponding authors.
Abstract
Background: Benzene (BZ) is a well-established hematotoxicant, and cigarette smoke (CS) is a major non-occupational source of BZ exposure. Although BZ and CS co-exposure commonly occurs in real-world settings, the mechanisms underlying their combined toxicity remain unclear. Objective: This study investigated whether BZ and CS co-exposure aggravates hematotoxicity and explored the potential involvement of the aryl hydrocarbon receptor AhR-NLRP3 signaling pathway. Methods: Sixty male Balb/c mice were divided into six groups: CON, BZ, CS, BZ + CS, BZ + CS + CH223191 (AhR inhibitor), and BZ + CS + MCC950 (NLRP3 inhibitor), and subjected to an 8-week sub-chronic exposure protocol. Peripheral blood parameters, bone marrow histopathology, AhR–NLRP3 signaling pathway-related protein expression, and circulating inflammatory cytokines (IL-1β, IL-6, and IL-18) were evaluated. Longitudinal outcomes and benzene × cigarette smoke interactions were analyzed using statistical models appropriate to the experimental design. Results: BZ and CS co-exposure produced more pronounced hematological alterations than either exposure alone and was accompanied by aggravated bone marrow injury. Formal factorial analysis revealed significant benzene × cigarette smoke interactions for RBC and HGB, with interaction contrasts indicating greater-than-additive reductions. In contrast, no significant interactions were detected for WBC, NEUT, or PLT. Co-exposure also upregulated AhR, NLRP3, and cleaved caspase-1 (p20), and elevated circulating IL-1β, IL-6, and IL-18. Significant benzene × cigarette smoke interactions were observed for all three cytokines, with interaction contrasts indicating greater-than-additive increases. Pharmacological inhibition of AhR or NLRP3 attenuated hematological alterations, inflammatory cytokine elevations, and pathway-related changes. Conclusions: BZ and CS co-exposure aggravates hematotoxicity, and AhR–NLRP3-related signaling may be involved in this process.
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BibTeX
@article{han2026benzene,
title = {{Benzene and cigarette smoke co-exposure exacerbates hematotoxicity involving the AhR–NLRP3 signaling pathway}},
author = {Liya Han and Baoyan Liu and Ziyang Xu and Xiaohan Yang and Qiong Ning and Qiang Jia and Jin He and Yong Wang},
journal = {Toxicology Reports},
year = {2026},
month = oct,
doi = {10.1016/j.toxrep.2026.102361},
url = {https://doi.org/10.1016/j.toxrep.2026.102361},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Benzene and cigarette smoke co-exposure exacerbates hematotoxicity involving the AhR–NLRP3 signaling pathway
AU - Liya Han
AU - Baoyan Liu
AU - Ziyang Xu
AU - Xiaohan Yang
AU - Qiong Ning
AU - Qiang Jia
AU - Jin He
AU - Yong Wang
PY - 2026
DA - 2026/10/22
JO - Toxicology Reports
DO - 10.1016/j.toxrep.2026.102361
UR - https://doi.org/10.1016/j.toxrep.2026.102361
AB - Background: Benzene (BZ) is a well-established hematotoxicant, and cigarette smoke (CS) is a major non-occupational source of BZ exposure. Although BZ and CS co-exposure commonly occurs in real-world settings, the mechanisms underlying their combined toxicity remain unclear. Objective: This study investigated whether BZ and CS co-exposure aggravates hematotoxicity and explored the potential involvement of the aryl hydrocarbon receptor AhR-NLRP3 signaling pathway. Methods: Sixty male Balb/c mice were divided into six groups: CON, BZ, CS, BZ + CS, BZ + CS + CH223191 (AhR inhibitor), and BZ + CS + MCC950 (NLRP3 inhibitor), and subjected to an 8-week sub-chronic exposure protocol. Peripheral blood parameters, bone marrow histopathology, AhR–NLRP3 signaling pathway-related protein expression, and circulating inflammatory cytokines (IL-1β, IL-6, and IL-18) were evaluated. Longitudinal outcomes and benzene × cigarette smoke interactions were analyzed using statistical models appropriate to the experimental design. Results: BZ and CS co-exposure produced more pronounced hematological alterations than either exposure alone and was accompanied by aggravated bone marrow injury. Formal factorial analysis revealed significant benzene × cigarette smoke interactions for RBC and HGB, with interaction contrasts indicating greater-than-additive reductions. In contrast, no significant interactions were detected for WBC, NEUT, or PLT. Co-exposure also upregulated AhR, NLRP3, and cleaved caspase-1 (p20), and elevated circulating IL-1β, IL-6, and IL-18. Significant benzene × cigarette smoke interactions were observed for all three cytokines, with interaction contrasts indicating greater-than-additive increases. Pharmacological inhibition of AhR or NLRP3 attenuated hematological alterations, inflammatory cytokine elevations, and pathway-related changes. Conclusions: BZ and CS co-exposure aggravates hematotoxicity, and AhR–NLRP3-related signaling may be involved in this process.
SN - 2214-7500
ER -