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.