Oral administration of aflatoxin G₁ induces chronic alveolar inflammation associated with lung tumorigenesis.
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.
['Liu|Chunping|C|', 'Shen|Haitao|H|', 'Yi|Li|L|', 'Shao|Peilu|P|', 'Soulika|Athena M|AM|', 'Meng|Xinxing|X|', 'Xing|Lingxiao|L|', 'Yan|Xia|X|', 'Zhang|Xianghong|X|']
D000284:Administration, Oral D000348:Aflatoxins D000818:Animals D063646:Carcinogenesis D002908:Chronic Disease D005260:Female D005786:Gene Expression Regulation D051547:Heme Oxygenase-1 D007249:Inflammation D008171:Lung Diseases D008565:Membrane Proteins D051379:Mice D008807:Mice, Inbred BALB C D016328:NF-kappa B D011650:Pulmonary Alveoli D050796:STAT3 Transcription Factor D013482:Superoxide Dismutase
Lung tumorigenesis Oxidative stress Alveolar type II cell COX-2 Chronic inflammation Aflatoxin G(1)