Early life inhalation exposure to mine tailings dust affects lung development

Mark L. Witten, Binh Chau, Eduardo Sáez, Scott A Boitano, Robert Clark Lantz

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Exposure to mine tailings dust from active and abandoned mining operations may be a very significant health hazard, especially to sensitive populations living in arid and semi-arid climates like the desert southwest of the US. It is anticipated that early life exposures during sensitive times of development can lead to adult disease. However, very few studies have investigated the effects of inhalation exposure to real world dusts during lung development. Using a mouse model, we have examined the effect(s) of inhalation of real world mine tailing dusts under three separate conditions: (1) Exposure only during in utero development (exposure of the pregnant moms) (2) exposure only after birth and (3) exposures that occurred continuously during in utero development, through gestation and birth until the mice reached adulthood (28 days old). We found that the most significant changes in lung structure and function were observed in male mice when exposure occurred continuously throughout development. These changes included increased airway hyper-reactivity, increased expression of epithelial to mesenchymal (EMT) transition protein markers and increased expression of cytokines related to eosinophils. The data also indicate that in utero exposures through maternal inhalation can prime the lung of male mice for more severe responses to subsequent postnatal exposures. This may be due to epigenetic alterations in gene regulation, immune response, molecular signaling, and growth factors involved in lung development that may make the neonatal lung more susceptible to continued dust exposure.

Original languageEnglish (US)
Pages (from-to)124-132
Number of pages9
JournalToxicology and Applied Pharmacology
Volume365
DOIs
StatePublished - Feb 15 2019

Fingerprint

Inhalation Exposure
Tailings
Dust
Lung
Inhalation
Desert Climate
Health hazards
Southwestern United States
Parturition
Maternal Exposure
Gene expression
Vulnerable Populations
Intercellular Signaling Peptides and Proteins
Eosinophils
Epigenomics
Cytokines
Pregnancy
Health
Proteins
Genes

Keywords

  • Lung development
  • Lung disease
  • Mine tailings dust

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Early life inhalation exposure to mine tailings dust affects lung development. / Witten, Mark L.; Chau, Binh; Sáez, Eduardo; Boitano, Scott A; Lantz, Robert Clark.

In: Toxicology and Applied Pharmacology, Vol. 365, 15.02.2019, p. 124-132.

Research output: Contribution to journalArticle

@article{0a4154dc915345fe929ecdf2467ccb87,
title = "Early life inhalation exposure to mine tailings dust affects lung development",
abstract = "Exposure to mine tailings dust from active and abandoned mining operations may be a very significant health hazard, especially to sensitive populations living in arid and semi-arid climates like the desert southwest of the US. It is anticipated that early life exposures during sensitive times of development can lead to adult disease. However, very few studies have investigated the effects of inhalation exposure to real world dusts during lung development. Using a mouse model, we have examined the effect(s) of inhalation of real world mine tailing dusts under three separate conditions: (1) Exposure only during in utero development (exposure of the pregnant moms) (2) exposure only after birth and (3) exposures that occurred continuously during in utero development, through gestation and birth until the mice reached adulthood (28 days old). We found that the most significant changes in lung structure and function were observed in male mice when exposure occurred continuously throughout development. These changes included increased airway hyper-reactivity, increased expression of epithelial to mesenchymal (EMT) transition protein markers and increased expression of cytokines related to eosinophils. The data also indicate that in utero exposures through maternal inhalation can prime the lung of male mice for more severe responses to subsequent postnatal exposures. This may be due to epigenetic alterations in gene regulation, immune response, molecular signaling, and growth factors involved in lung development that may make the neonatal lung more susceptible to continued dust exposure.",
keywords = "Lung development, Lung disease, Mine tailings dust",
author = "Witten, {Mark L.} and Binh Chau and Eduardo S{\'a}ez and Boitano, {Scott A} and Lantz, {Robert Clark}",
year = "2019",
month = "2",
day = "15",
doi = "10.1016/j.taap.2019.01.009",
language = "English (US)",
volume = "365",
pages = "124--132",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Early life inhalation exposure to mine tailings dust affects lung development

AU - Witten, Mark L.

AU - Chau, Binh

AU - Sáez, Eduardo

AU - Boitano, Scott A

AU - Lantz, Robert Clark

PY - 2019/2/15

Y1 - 2019/2/15

N2 - Exposure to mine tailings dust from active and abandoned mining operations may be a very significant health hazard, especially to sensitive populations living in arid and semi-arid climates like the desert southwest of the US. It is anticipated that early life exposures during sensitive times of development can lead to adult disease. However, very few studies have investigated the effects of inhalation exposure to real world dusts during lung development. Using a mouse model, we have examined the effect(s) of inhalation of real world mine tailing dusts under three separate conditions: (1) Exposure only during in utero development (exposure of the pregnant moms) (2) exposure only after birth and (3) exposures that occurred continuously during in utero development, through gestation and birth until the mice reached adulthood (28 days old). We found that the most significant changes in lung structure and function were observed in male mice when exposure occurred continuously throughout development. These changes included increased airway hyper-reactivity, increased expression of epithelial to mesenchymal (EMT) transition protein markers and increased expression of cytokines related to eosinophils. The data also indicate that in utero exposures through maternal inhalation can prime the lung of male mice for more severe responses to subsequent postnatal exposures. This may be due to epigenetic alterations in gene regulation, immune response, molecular signaling, and growth factors involved in lung development that may make the neonatal lung more susceptible to continued dust exposure.

AB - Exposure to mine tailings dust from active and abandoned mining operations may be a very significant health hazard, especially to sensitive populations living in arid and semi-arid climates like the desert southwest of the US. It is anticipated that early life exposures during sensitive times of development can lead to adult disease. However, very few studies have investigated the effects of inhalation exposure to real world dusts during lung development. Using a mouse model, we have examined the effect(s) of inhalation of real world mine tailing dusts under three separate conditions: (1) Exposure only during in utero development (exposure of the pregnant moms) (2) exposure only after birth and (3) exposures that occurred continuously during in utero development, through gestation and birth until the mice reached adulthood (28 days old). We found that the most significant changes in lung structure and function were observed in male mice when exposure occurred continuously throughout development. These changes included increased airway hyper-reactivity, increased expression of epithelial to mesenchymal (EMT) transition protein markers and increased expression of cytokines related to eosinophils. The data also indicate that in utero exposures through maternal inhalation can prime the lung of male mice for more severe responses to subsequent postnatal exposures. This may be due to epigenetic alterations in gene regulation, immune response, molecular signaling, and growth factors involved in lung development that may make the neonatal lung more susceptible to continued dust exposure.

KW - Lung development

KW - Lung disease

KW - Mine tailings dust

UR - http://www.scopus.com/inward/record.url?scp=85060111199&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060111199&partnerID=8YFLogxK

U2 - 10.1016/j.taap.2019.01.009

DO - 10.1016/j.taap.2019.01.009

M3 - Article

VL - 365

SP - 124

EP - 132

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

ER -