Binding of tritiated dehydroretronecine to macromolecules.

In vivo and in vitro experiments have shown that the pyrrolizidine alkaloid metabolite dehydroretronecine binds readily to macromolecules. In the in vivo experiment there was a preferential binding of dehydroretronecine to the gastric mucosa. Further extraction of the mucosa revealed a large percentage of the 3H was bound to the protein fraction and to a much lesser extent to DNA and RNA. The influence of pH on the binding of dehydroretronecine was substantiated in the in vitro experiment. Dehydroretronecine bound to calf thymus DNA and bovine serum albumin most readily under acidic conditions. These data suggest a direct correlation of the levels of dehydroretronecine binding to cellular macromolecules with the lesions that develop in affected organs.