Impairment of alveolar type-II cells involved in the toxicity of Aflatoxin G1 in rat lung

Our previous studies showed intragastric administration of Aflatoxin G1 (AFG1) could induce lung adenocarcinoma, which derived from alveolar type II cells (AT-II cells). AT-II cells contribute to Aflatoxin B1 (AFB1) metabolism and also serve as the potential progenitor cells for AFB1-induced tumorigenesis. Thus, AT-II cells may constitute a target for AFG1 exposure and serve as progenitor cells for tumorigenesis induced by AFG1. The current experiment was designed to identify the acute toxicity of AFG1 in AT-II cells following a single intratracheal administration of AFG1. We observed inflammatory changes in the alveolar septum at days 3 and 7 after AFG1 treatment, which resolved by 14 days. We also found AFG1 caused lamellar bodies damage in AT-II cells at days 3 and 7 post-treatment. Surfactant protein C (SP-C) expression, an AT-II cell-specific marker, was reduced at day 7 post-treatment. The structural and functional impairment in AT-II cells returned to normal by day 14. Moreover, we found that AFG1 induced a elevation of intracellular calcium concentration [Ca2+]i in AT-II cells in vitro, which may contribute to the decreased SP-C expression. In conclusion, our results show AFG1 induces structural and functional impairment in AT-II cells involved in the acute toxicity of AFG1 in lung.