Abstract |
Allylisopropylacetamide (AIA) did not cause DNA damage in rat liver. The porphyrinogenic research drug did strongly induce the activity (25-fold) of rat hepatic enzyme ornithine decarboxylase (ODC). By either the oral or the subcutaneous route AIA produced a long lasting induction (30-40 hr) of hepatic ODC activity. Four analogs of AIA, 2-propyl-2-isopropylacetamide (PIA), allobarbital, allylbenzene and allylacetate were examined for their ability to induce hepatic ODC. PIA, allylbenzene and allobarbital were active ODC inducers while allylacetate was not. Although induction of hepatic ALA synthetase activity and the accumulation of hepatic porphyrins depends on the allyl moiety of AIA, this was not the case with hepatic ODC induction. AIA did not elevate serum alanine aminotransferase (SGPT), and thus hepatic cell death is not a likely explanation of AIA's long lasting induction of ODC. As AIA does not belong in any of the common categories of ODC inducers, it is possible that AIA may be the chemical prototype of a new class of hepatic ODC inducers. |