Genotoxic and cytokine-associated responses to benzo[g,h,i]perylene and benzo[b]fluoranthene in a human lung co-culture model at the pseudo-air-liquid interface.

Authors

Matjaž Novak, Martina Štampar, Alja Štern, Michael J Burgum, Gillian E Conway, Goran Gajski, Shareen H Doak, Bojana Žegura

Published in

Toxicology. Pages 154607. Oct 02, 2026. Epub Oct 02, 2026.

Abstract

Polycyclic aromatic hydrocarbons (PAHs), including benzo[g,h,i]perylene (BGP) and benzo[b]fluoranthene (BBF), are ubiquitous airborne pollutants with significant toxicological relevance. Inhalation represents the primary exposure route, with the respiratory epithelium and alveolar macrophages serving as key targets for adverse effects. Despite their prevalence, mechanistic data on BGP and BBF, particularly in respiratory cell models, remain limited. Here, we evaluated the cytotoxic, genotoxic, and cytokine-associated effects of BGP and BBF in a co-culture of human alveolar epithelial (A549) and macrophage-like differentiated (dTHP-1) cells maintained at a pseudo-air-liquid interface (pseudo-ALI). No detectable genotoxic effects were observed following 24h exposure to non‑cytotoxic concentrations of BGP (≤ 18.1µM) and BBF (≤ 39.6µM), as evidenced by the absence of DNA double‑strand breaks, phospho‑histone H3 activation, and micronucleus formation. In contrast, both compounds modulated several inflammatory cytokine-associated endpoints, with BGP producing a stronger effect than BBF. BGP significantly increased IL-8 secretion and the proportion of cells expressing TNF-α, IL-6, and IL-1β, while BBF moderately elevated the proportion of cells expressing TNF-α, IL-6, and IFN-γ. Targeted qPCR analysis detected changes in selected cytokine-associated genes. These findings indicate that BGP, and to a lesser extent BBF, modulated selected inflammatory cytokines without detectable DNA damage under the tested conditions. Limited metabolic activation may have contributed to the negative genotoxicity findings; however, metabolic activity and PAH metabolite formation were not assessed in this co-culture. The results highlight inflammatory cytokine-associated effects, particularly following BGP exposure, and demonstrate the value of the A549/dTHP-1 co-culture for investigating early cellular responses to PAHs.

PMID:
42826830
Bibliographic data and abstract were imported from PubMed on 03 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.