Metabolism, DNA Binding and Cytotoxicity of Aflatoxin B1 in Tracheal Explants from Syrian Hamster
Metabolism, DNA binding and cytopathological effects of aflatoxin B1 (AFB1) were studied in isolated tracheal explants from Syrian golden hamster. Explants were exposed to 0.1, 0.5 and 1.0 μM [14C]AFB1 in Dulbecco's modified Eagle medium for 24 h, then analyzed for AFB1-DNA binding and AFB1 metabolism. Binding (pmol AFB1/mg DNA) was dose-related (16.3 ± 1.9 to 180.8 ± 16.1) and analysis of the culture medium revealed the metabolic conversion products aflatoxicol (AFL) and aflatoxin Q1 (AFQ1). Ultrastructural analysis of sections of tracheal epithelium revealed degenerative changes primarily in the non-ciliated epithelial cells. Autoradiographic analysis of the same treated explants, however, showed no discernible distribution of label with respect to either cell type or cell location, with the exception of increased grain densities overlying vacuoles containing dark droplets. In addition, S9 prepared from hamster trachea was shown to activate AFB1 to mutagens detectable by Salmonella typhimurium TA 98, but was approximately 70 times less active on a per mg protein basis than was S9 prepared from hamster liver. These results demonstrate the metabolic capabilities of tracheal epithelial cells in the activation of AFB1, thus indicating that AFB1 present in respiratory particles may be activated by pulmonary mixed-function oxidases, posing a hazard to those exposed.
Coulombe, R.A., D.W. Wilson and D.P.H. Hsieh (1984). Metabolism, DNA binding and cytotoxicity of aflatoxin B1 in tracheal explants from Syrian hamsters. Toxicology 32:117-130.