Elsevier

Environmental Pollution

Volume 226, July 2017, Pages 412-425
Environmental Pollution

Exposure scenario: Another important factor determining the toxic effects of PM2.5 and possible mechanisms involved

https://doi.org/10.1016/j.envpol.2017.04.010Get rights and content

Highlights

  • The mode of exposure impacted the PM2.5-induced toxic effects and cellular responses.

  • Acute exposure to high dose of PM2.5 resulted in cellular metabolic dysfunction and necrosis.

  • Repeated exposure to low dose of PM2.5 led to the activation of survival pathways and cellular pathogenic adaptation.

Abstract

Worsening air pollution is a serious threat to public health in many urban and heavily industrialized areas. Particle size and chemical composition are well known determinants of the pathological response to air pollution. In addition, pathological responses may depend on the exposure profile (or scenario) of air pollution. For instance, we previously demonstrated that repeated exposure to low levels of fine airborne particulate matter (PM2.5) induced distinct epigenetic changes compared to acute high-doses exposure. In the present study, we evaluated the differential pathological responses of BEAS-2B human bronchial epithelial cells to two distinct PM2.5 exposure scenarios: 24-h exposure to high-doses PM2.5 (0, 6, 12, 24, 48, 96 μg/cm2) and 10 days’ repeated exposure to low levels of PM2.5 (0, 1.5, 3, 6 μg/cm2). Acute exposure to high concentrations of PM2.5 caused ROS burst, marked DNA damage, dysfunction of the endoplasmic reticulum (ER) stress response, autophagy and necrotic cell death. In contrast, repeated low levels of PM2.5 led to sustained low-grade ROS accumulation, milder DNA damage, ER stress/unfolded protein response (UPR), S-phase arrest, apoptosis, and autophagy. Notably, most cells surviving repeated low-level exposure showed a series of abnormal adaptive responses, such as inhibition of mitochondria biogenesis and epigenetic dysregulation. These results indicate that different PM2.5 exposure scenarios induce distinct forms cytotoxicity and adaptive response. In addition to particle size and chemical composition, exposure scenario may be a critical factor determining the toxic health effects of PM2.5.

Introduction

Air pollution by ambient particulate matter has become one of the most serious environmental and public health challenges in many developing and developed countries. In particular, increasing airborne fine particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) has a profound impact on public health (Zhang et al., 2015). In some areas of north China, the annual mean concentration of PM2.5 has reached about 100 μg/m3; over the last few years (Xie et al., 2015, Zheng et al., 2015). People living in these long-polluted areas are more likely to be in a long-term, slightly polluted PM2.5 exposure scenario (repeated exposure). In addition, acute haze episodes or smog events with high concentrations of PM2.5 (more than 500 μg/m3, sometimes over 1000 μg/m3) now occur frequently in some areas (Guan et al., 2014). Therefore, the population may be subjected to two distinct PM2.5 exposure scenarios, repeated low-level and short-term high-level exposure, with different health effects.

Exposure to PM2.5, including both acute exposure at extremely high levels and repeated exposure at lower levels, is strongly associated with many pulmonary diseases (Lelieveld et al., 2015, Young et al., 2014). Previous studies have indicated that even short-term (several hours) exposure to extremely high levels of PM2.5 can induce acute inflammation of the respiratory tract and acute exacerbation of cardiopulmonary diseases, such as asthma and acute paroxysm of chronic bronchitis (Khafaie et al., 2016, Marino et al., 2015, Yamauchi et al., 2016). Accumulating evidence has demonstrated that long-term low-level PM2.5 exposure can also contribute to a variety of chronic pulmonary diseases, including chronic obstructive pulmonary disease (COPD), fibrosis and even lung cancer (Benmerad et al., 2015, Hamra et al., 2014, Khafaie et al., 2016).

However, the exact mechanisms underlying PM2.5-induced pulmonary diseases are not well-known, and it is unclear whether PM2.5 induces similar toxicity mechanisms under different exposure scenarios. Most in vitro experiments have focused on the adverse effects of short-term PM2.5 exposure to high concentrations (Ding et al., 2014, Vattanasit et al., 2014, Yang et al., 2015), but the toxicity mechanisms obtained may be different from those induced by long-term low-level exposure and thus do not provide an accurate model of PM2.5-induced disease. Recently, some researchers have posited that the PM2.5 response exhibits hormesis, defined as an inverted U-shaped or J-shaped dose-response relationship (Cox, 2012). Several studies have demonstrated that long-term low-level exposure to particles or nanoparticles elicits dissimilar biological responses compared to short-term high-level exposure (Vales et al., 2015, Zhou et al., 2016). All these findings suggest that in addition to particle size and chemical composition, exposure scenario may be an important factor determining the toxic effects of PM2.5.

ROS-mediated oxidative stress is believed to play a crucial role in PM2.5-induced cytotoxicity (Xia et al., 2007), and the kinetics of ROS accumulation depend on the characteristics of PM2.5 exposure, such as duration and particle concentration. Intracellular ROS could thus serve as a biological signal to elicit different responses, including reparative/adaptive and pathogenic responses (Dioni et al., 2011, Schumacker, 2015, Shadel and Horvath, 2015). It has been reported that ROS-induced oxidative stress injuries, such as DNA damage and repair, cell death, inflammation and epigenetic regulation, vary with different PM2.5 exposure scenarios (Gao et al., 2016, Longhin et al., 2013, Zhou et al., 2016). The hypothesis addressed in the present study is that even brief exposure to higher concentrations of PM2.5 induces extensive ROS-mediated oxidative damage that overwhelms endogenous defense mechanisms, causing injury and metabolic collapse in a short time, while repeated exposure to low PM2.5 levels causes chronic and low-grade enhancement of ROS, which triggers cycles of perturbation/damages and repairs mediated by adaptive responses.

We thus compared the responses of the human bronchial epithelial cell line BEAS-2B to two distinct PM2.5 exposure scenarios to examine whether exposure is an important parameter determining the health effects of PM2.5. The prospective findings of our study could offer new insight into the pathogenesis of diseases caused by PM2.5 exposure.

Section snippets

Preparation of PM2.5 suspension and cell exposure

The PM2.5 used in this study was collected from Wuhan, China. The specific methods for PM2.5 collection, extraction, and characterization, and the detailed characteristics of the sampling site were described in our previous report (Yuan et al., 2015, Zhou et al., 2016). PM2.5 suspensions were freshly prepared before each application. Briefly, PM2.5 was re-suspended in Dulbecco's Modified Eagle's Medium (DMEM, Gibco, USA) containing 2% fetal bovine serum (FBS, Gibco) and the solution was

Exposure models

The doses used in this study are based on real-world exposure scenarios revealed by MPPD software (de Winter-Sorkina and Cassee, 2003, Gangwal et al., 2011). Air quality is closely associated with PM2.5 concentration. The concentrations of 100, 200, 500 and 1000 μg/m3 were corresponding to lightly, moderately, heavily, and severely polluted, respectively. The MPPD software provides more precise calculations of the actual deposition, clearance, and retention of PM2.5 on epithelium. The total

Discussion

The increasing severity of air pollution in certain regions, especially airborne fine particulate matter (PM2.5), is strongly linked to the incidence of respiratory diseases (Coogan et al., 2012, Hamra et al., 2014, Rice et al., 2016). In recent years, numerous studies have characterized the toxicity of PM2.5 and explored the underlying cellular mechanisms to provide a detailed explanation of the initiation and development of PM2.5-induced diseases. However, there is still no consensus on PM2.5

Conclusion

In summary, one of most intriguing implications of our data is that PM2.5 can cause distinct toxic effects under different exposure conditions. Acute high-dose exposure overwhelms anti-oxidative capacity and the ability to clear damaged constituents by autophagic flux, resulting in necrosis and inflammation. In contrast, most cells may have sufficient capacity to survive mild sustained exposure, while the few dying cells are cleared by apoptosis, obviating inflammation. However, accumulation of

Funding sources

This work was supported by National Key Basic Research Program of China (973 Program; No. 2011CB503803), the National Natural Science Foundation of China (No. 81430090), and Beijing Key Laboratory of Environmental Toxicology (No. 2016HJDL04).

References (58)

  • P.T. Schumacker

    Reactive oxygen species in cancer: a dance with the devil

    Cancer Cell

    (2015)
  • L.A. Sena et al.

    Physiological roles of mitochondrial reactive oxygen species

    Mol. Cell

    (2012)
  • G.S. Shadel et al.

    Mitochondrial ROS signaling in organismal homeostasis

    Cell

    (2015)
  • H. Tian et al.

    DNA damage response–a double-edged sword in cancer prevention and cancer therapy

    Cancer Lett.

    (2015)
  • U. Vattanasit et al.

    Oxidative DNA damage and inflammatory responses in cultured human cells and in humans exposed to traffic-related particles

    Int. J. Hyg. Environ. Health

    (2014)
  • Y. Xie et al.

    Spatiotemporal variations of PM2. 5 and PM10 concentrations between 31 Chinese cities and their relationships with SO2, NO2, CO and O3

    Particuology

    (2015)
  • A. Collins et al.

    Comet assay in human biomonitoring studies: reliability, validation, and applications

    Environ. Mol. Mutagen

    (1997)
  • P.F. Coogan et al.

    Air pollution and incidence of hypertension and diabetes mellitus in black women living in Los Angeles

    Circulation

    (2012)
  • E.M. Cottam et al.

    Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate

    Autophagy

    (2011)
  • L.A. Cox

    Hormesis for fine particulate matter (PM 2.5)

    Dose Response

    (2012)
  • R. de Winter-Sorkina et al.

    From Concentration to Dose: Factors Influencing Airborne Particulate Matter Deposition in Humans and Rats

    (2003)
  • L. Dioni et al.

    Effects of short-term exposure to inhalable particulate matter on telomere length, telomerase expression, and telomerase methylation in steel workers

    Environ. Health Perspect.

    (2011)
  • J. Espada et al.

    Epigenetic disruption of ribosomal RNA genes and nucleolar architecture in DNA methyltransferase 1 (Dnmt1) deficient cells

    Nucleic Acids Res.

    (2007)
  • S. Gangwal et al.

    Informing selection of nanomaterial concentrations for ToxCast in vitro testing based on occupational exposure potential

    Environ. Health Perspect.

    (2011)
  • Z.X. Gao et al.

    Assessment of DNA damage and cell senescence in corneal epithelial cells exposed to airborne particulate matter (PM2.5) collected in guangzhou, China

    Invest Ophthalmol. Vis. Sci.

    (2016)
  • D. Guan et al.

    The socioeconomic drivers of China's primary PM2. 5 emissions

    Environ. Res. Lett.

    (2014)
  • M.A. Hahn et al.

    Methylation of polycomb target genes in intestinal cancer is mediated by inflammation

    Cancer Res.

    (2008)
  • G.B. Hamra et al.

    Outdoor particulate matter exposure and lung cancer: a systematic review and meta-analysis

    Environ. Health Perspect.

    (2014)
  • M. Hariri et al.

    Biogenesis of multilamellar bodies via autophagy

    Mol. Biol. Cell

    (2000)
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