Oral administration of aflatoxin G1 induces chronic alveolar inflammation associated with lung tumorigenesis

Chunping Liu, Haitao Shen, Li Yi, Peilu Shao, Athena Soulika, Xinxing Meng, Lingxiao Xing, Xia Yan, Xianghong Zhang

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Our previous studies showed oral gavage of aflatoxin G1 (AFG1) induced lung adenocarcinoma in NIH mice. We recently found that a single intratracheal administration of AFG1 caused chronic inflammatory changes in rat alveolar septum. Here, we examine whether oral gavage of AFG1 induces chronic lung inflammation and how it contributes to carcinogenesis. We evaluated chronic lung inflammatory responses in Balb/c mice after oral gavage of AFG1 for 1, 3 and 6 months. Inflammatory responses were heightened in the lung alveolar septum, 3 and 6 months after AFG1 treatment, evidenced by increased macrophages and lymphocytes infiltration, up-regulation of NF-κB and p-STAT3, and cytokines production. High expression levels of superoxide dismutase (SOD-2) and hemoxygenase-1 (HO-1), two established markers of oxidative stress, were detected in alveolar epithelium of AFG1-treated mice. Promoted alveolar type II cell (AT-II) proliferation in alveolar epithelium and angiogenesis, as well as increased COX-2 expression were also observed in lung tissues of AFG1-treated mice. Furthermore, we prolonged survival of the mice in the above model for another 6 months to examine the contribution of AFG1-induced chronic inflammation to lung tumorigenesis. Twelve months later, we observed that AFG1 induced alveolar epithelial hyperplasia and adenocarcinoma in Balb/c mice. Up-regulation of NF-κB, p-STAT3, and COX-2 was also induced in lung adenocarcinoma, thus establishing a link between AFG1-induced chronic inflammation and lung tumorigenesis. This is the first study to show that oral administration of AFG1 could induce chronic lung inflammation, which may provide a pro-tumor microenvironment to contribute to lung tumorigenesis.

Original languageEnglish (US)
Pages (from-to)547-556
Number of pages10
JournalToxicology Letters
Volume232
Issue number3
DOIs
StatePublished - Feb 3 2015

Keywords

  • Aflatoxin G
  • Alveolar type II cell
  • Chronic inflammation
  • COX-2
  • Lung tumorigenesis
  • Oxidative stress

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Oral administration of aflatoxin G<sub>1</sub> induces chronic alveolar inflammation associated with lung tumorigenesis'. Together they form a unique fingerprint.

  • Cite this