Cell proliferation in nasal respiratory epithelium of people exposed to urbanpollution

Calderón‐Garcidueñas, Lilian; Rodrı́guez-Alcaraz, Antonio; Garcı́a, Raquel; Mejía, Gerardo Barragán; Villarreal-Calderón, Anna; Madden, Michael C.

doi:10.1093/carcin/20.3.383

Cited by 27 publications

(23 citation statements)

References 60 publications

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“…Ki67 is a proliferation marker and a known driver of the cell cycle (Szabo, 2001). Increased proliferation in airway epithelial cells is considered to be a reliable indicator of many airborne chemical toxicants (Calderón-Garcidueñas et al, 1999). Our present finding is also in contrast with that observed in vivo following airborne insults.…”

Section: Discussioncontrasting

confidence: 84%

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

Iskandar

Mathis

Martin

et al. 2017

ALTEX

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ratory animals -to reduce the number of animals, to refine the design of procedures such that pain and distress are minimized, and to replace animal models with alternative methods and lower organisms when possible (Doke and Dhawale, 2015). In this regard, the capability to preserve human respiratory cells in culture provides a tool not only to generate mechanistic data, but also to improve the predicted effects of exposure hazard through inhalation in humans. An emphasis on assessment studies using human-derived in vitro culture systems will reduce the problems that are inherent to interspecies translatability (Manuppello and Sullivan, 2015).In vitro toxicology approaches have evolved from focusing on the molecular changes within a cell to understanding the toxicity-related mechanisms (cell-cell interactions) in models IntroductionMechanistic investigation of the impact of exposure on the lower airway remains challenging because access to lung tissues is limited. Although biopsy samples can be obtained from patients/donors for mechanistic studies of exposure-induced injury, a biopsy procedure is invasive and there are related ethical concerns (Peppercorn, 2013). Alternatively, animal studies allow the collection of biological samples from various animal models of human diseases. However, biological responses can vary among animal species, and findings obtained from animal studies may not apply to humans. Alternatives to animal testing have been proposed to overcome these drawbacks, including the 3Rs strategy -reduction, refinement, and replacement of labo- Research SummaryIn vitro toxicology approaches have evolved from a focus on molecular changes within a cell to understanding of toxicity-related mechanisms in systems that can mimic the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offers a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus, the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure. The present study investigated further the application of in vitro human 3-D nasal epithelial culture models for toxicological assessment of inhalation exposure. Aligned with 3Rs strategy, this study aimed to explore the relevance of a human 3-D nasal culture model to assess the toxicological impact of aerosols generated from a candidate modified risk tobacco product (cMRTP), the Tobacco Heating System (THS) 2.2, as compared with smoke generated from reference cigarette 3R4F. A series of experimental repetitions, where multiple concentrations of THS2.2 aerosol and 3R4F smoke were applied, were conducted to obtain reproducible measurements to understand the cellular/molecular changes that occur following exposure. In agreement with "Toxicity Testing in the 21 st Century -a Vision and a Strategy", this study implemented a systems toxicology approach and found that for all tested concentrations the impa...

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Section: Discussioncontrasting

confidence: 84%

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

Iskandar

Mathis

Martin

et al. 2017

ALTEX

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“…The atmosphere in Southwest Metropolitan Mexico City (SWMMC), is characterized by > 4 hours/day with O 3 > 0.08 ppm, average maximal peaks of 0.250 ppm, and high ozone concentrations up to 0.48 ppm (24). Both PM 10 and PM 2.5 routinely exceed their respective annual arithmetic means above the current annual US standards (PM 10 (12,14). Other pollutants detected in SWMMC include formaldehyde and acetaldehyde concentrations in the range of 5.9-110 and 2-67 parts per billion per volume (ppbv), respectively; maximal peaks are recorded between 8 and 10 am for acetaldehyde and 10 am to 12 pm for formaldehyde (1).…”

Section: Study Areamentioning

confidence: 99%

Nasal Biopsies of Children Exposed to Air Pollutants

et al. 2001

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Southwest Metropolitan Mexico City (SWMMC) atmosphere is a complex mixture of air pollutants, including ozone, particulate matter, and aldehydes. Children in SWMMC are exposed chronically and sequentially to numerous toxicants, and they exhibit signi cant nasal damage. The objective of this study was to assess p53 accumulation by immunohistochemistr y in nasal biopsies of SWMMC children. We evaluated 111 biopsies from 107 children (83 exposed SWMMC children and 24 control children residents in a pollutant-compliant Caribbean island). Complete clinical histories and physical examinations, including an ear-nose-throat (ENT) exam were done. There was a signi cant statistical difference in the upper and lower respiratory symptomatolog y and ENT ndings between control and exposed children ( p < 0.001). Control children gave no respiratory symptomatolog y in the 3 months prior to the study; their biopsies exhibited normal ciliated respiratory epithelium and were p53-negative . SWMMC children complained of epistaxis, nasal obstruction, and crusting. Irregular areas of whitish-gray recessed mucosa over the inferior and middle turbinates were seen in 25% of SWMMC children, and their nasal biopsies displayed basal cell hyperplasia, decreased numbers of ciliated and goblet cells, neutrophilic epithelial in ltrates, squamous metaplasia, and mild dysplasia. Four of 21 SWMMC children with grossly abnormal mucosal changes exhibited strong transmural nuclear p53 staining in their nasal biopsies (p 0.005, odds ratio 26). In the context of lifetime exposures to toxic and potentially carcinogenic air pollutants, p53 nasal induction in children could potentially represent. a) a checkpoin t response to toxic exposures, setting up a selective condition for p53 mutation, or b) a p53 mutation has already occurred as a result of such selection. Because the biological signi cance of p53 nuclear accumulation in the nasal biopsies of these children is not clear at this point, we strongly suggest that children with macroscopic nasal mucosal abnormalities should be closely monitored by the ENT physician. Parents should be advised to decrease the children's number of outdoor exposure hours and encourage a balanced diet with an important component of fresh fruits and vegetables.

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“…Computational model of nose anatomy has shown high wall shear stresses just breathing (Elad et al, 2005). In addition to these aerodynamic reasons, the larger occurrence of this epithelium at the rostral half may be explained because inflow is more aggressive than outflow as it is colder, drier, and brings biological and chemical hazards, as described for air pollutants (Calderón-Garcidueñ as et al, 1999;Cho et al, 1999). Our results lead us to suggest that these normal aggressions of airflow are sufficient to develop metaplastic epithelium in control animals, as a normal feature of their nasal fossae.…”

Section: Discussionmentioning

confidence: 54%

Histological changes in rat nasal epithelia after unilateral neonatal naris occlusion

Cámara

Garrosa

Gayoso

2006

Microscopy Res & Technique

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The authors studied the extent of the different epithelia lining the nasal fossae of the albino rat after neonatal closure of one naris. Newborn pups were anesthetized by hypothermia and the external opening of their right naris cauterized, while littermates served as controls. Animals were sacrificed at 3 months, and the occluded (OCF) and nonoccluded (NOF) fossae of experimental animals as well as both fossae of control animals (CTF) were histologically studied. In both control and experimental animals, nasal fossae were lined by five different types of epithelia: squamous stratified, transitional, metaplastic, respiratory, and olfactory epithelia. It was found that closure of one naris provokes reorganization of the epithelial lining in both the occluded and nonoccluded side. In CTF airflow, physical conditions as well as pollutants and biological agents irritate the epithelial lining, causing squamous metaplasia as well as metaplastic epithelium showing inflammation in rostral levels. In CTF caudal levels, the metaplastic epithelium appears to a lesser degree and the respiratory epithelium prevails, except for the most caudal level where the olfactory epithelium is prevalent. In OCF, the protected environment created prevents the occurrence of metaplastic epithelium, the transitional, respiratory, and olfactory epithelia developing in the corresponding area instead. In NOF, where the airflow is double, the same pattern occurs as in CTF, although metaplastic epithelium values are approximately double, suggesting a clear linear effect. An outstanding feature observed was the increased extent of the olfactory epithelium in OCF regarding NOF, although changes in its morphological structure were not found. Airflow properties, including pressure, coldness, velocity, and turbulence, as well as biological and chemical hazards present in inflow, cause histological reorganization of the nasal epithelium lining during postnatal development. Results prove the need to consider airflow changes in nasal fossae surgery and point to the protective value of naris closure in ENT clinics, supporting it as a treatment of atrophic rhinitis.

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Cell proliferation in nasal respiratory epithelium of people exposed to urbanpollution

Cited by 27 publications

References 60 publications

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product

Nasal Biopsies of Children Exposed to Air Pollutants

Histological changes in rat nasal epithelia after unilateral neonatal naris occlusion

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