Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Background: Precision-cut lung slices (PCLS) are slices of the lung cultured ex vivo that facilitates the evaluation of various chemical agents on the lung. The anti-tumor drug bleomycin causes drug-induced interstitial pneumonia, but the mechanism is not clear.
Aims: To determine the mechanism by which bleomycin induces cytotoxicity and fibrosis in PCLS.
Methods: iUIP lungs were used for qPCR analysis. iUIP lungs were used to generate PCLS. PCLS treated with bleomycin were analyzed for cytotoxicity and histopathology.
Results: Perinuclear localization of γH2AX was observed only in PCLS of iUIP lung, whereas γH2AX-psotive cells were observed in bleomycin treated with PCLS of normal lung and iUIP lungs. In addition, Tunel-positive cells were observed in bleomycin treated PCLS of iUIP lungs. An increase in Col1a1 as a fibrosis marker was not detected by bleomycin treatment.
Conclusions: The iUIP lung were more senescent than in WT. Thus, an ability of DNA repair may be impaired in iUIP lungs. Indeed, bleomycin treatment of PCLS in iUIP lungs resulted in more cell death with failure of DNA repair. Although bleomycin does not act directly on fibrosis, it may promote fibrosis through secondary effects such as inflammation via robust cell death.
