The Carcinogenic Properties of Overlooked yet Prevalent Polycyclic Aromatic Hydrocarbons in Human Lung Epithelial Cells

Abstract

The WHO classified air pollution as a human lung carcinogen and polycyclic aromatic hydrocarbons (PAHs) are components of both indoor (e.g., tobacco smoke and cookstoves) and outdoor (e.g., wildfires and industrial and vehicle emissions) air pollution, thus a human health concern. However, few studies have evaluated the adverse effects of low molecular weight (LMW) PAHs, the most abundant PAHs in the environment. We hypothesized that LMW PAHs combined with the carcinogenic PAH benzo[a]pyrene (B[a]P) act as co-carcinogens in human lung epithelial cell lines (BEAS-2B and A549). Therefore, in this paper, we evaluate several endpoints, such as micronuclei, gap junctional intercellular communication (GJIC) activity, cell cycle analysis, anti-BPDE-DNA adduct formation, and cytotoxicity after mixed exposures of LMW PAHs with B[a]P. The individual PAH doses used for each endpoint did not elicit cytotoxicity nor cell death and were relevant to human exposures. The addition of a binary mixture of LMW PAHs (fluoranthene and 1-methylanthracene) to B[a]P treated cells resulted in significant increases in micronuclei formation, dysregulation of GJIC, and changes in cell cycle as compared to cells treated with either B[a]P or the binary mixture alone. In addition, anti-BPDE-DNA adducts were significantly increased in human lung cells treated with B[a]P combined with the binary mixture of LMW PAHs as compared to cells treated with B[a]P alone, further supporting the increased co-carcinogenic potential by LMW PAHs. Collectively, these novel studies using LMW PAHs provide evidence of adverse pulmonary effects that should warrant further investigation.

Exposure to Benzo[a]pyrene and 1-Nitropyrene in Particulate Matter Increases Oxidative Stress in the Human Body

“…Addition of LMW PAHs to BaP-treated cells significantly increased micronucleus formation, gap junctional intercellular communication (GJIC) dysregulation, and cell cycle alterations compared to BaP alone. In addition, human lung cells treated with a binary mixture of B[a]P and LMW PAHs showed a significant increase in anti-BPDE-DNA adducts compared to cells treated with BaP alone, indicating that LMW PAHs have increased cocarcinogenic potential [24]. Romo et al (2019) revealed that non-genotoxic, low-molecularweight (LMW) PAHs trigger the activation of mitogen-activated protein kinase pathways and lead to the secretion of inflammatory mediators [25].…”

Contribution of Road Vehicle Tyre Wear to Microplastics and Ambient Air Pollution

“…Of the aforementioned substances present in tyres, Zn can be toxic to living organisms [131,132], butadiene is considered carcinogenic to humans [133], benzothiazoles and derivatives are carcinogens and genotoxicants [134], and PAHs are toxic [135] and carcinogenic [136]. Recently, a transformation product of 6-PPD was linked to the acute mortality of coho salmon [137], and the same chemical was shown to shorten the lifespan and health span of Caenorhabditis elegans an in vitro study [138,139].…”

Kernel extreme learning with harmonized bat algorithm for prediction of pyrene toxicity in rats

“…Polycyclic aromatic hydrocarbons (PAHs) are frequently toxic in indoor and outdoor sources. 1 Pyrene comprises four fused benzene rings and is among the most thoroughly investigated PAHs. It is commonly employed as a model substance in research on the toxicology of PAHs.…”