Mimetics of L-histidinol which selectively modulate daunomycin toxicity in normal and tumorigenic epithelial cells.

In the accompanying publication, it was shown that L-histidinol protected the normal Madin-Darby, canine kidney (MDCK) epithelial cell line from daunomycin (DA U) toxicity, but enhanced DAU toxicity in MDCK-T1, a tumorigenic derivative of MDCK. The protection of MDCK cells from DAU by L-histidinol was also shown to be independent of its ability to inhibit protein synthesis. Here, clonogenic cell survival assay's show, that imidazole was as effective as L-histidinol in protecting MDCK cells from DAU, but had less impact on MDCK-T1 line. Certain antieicosanoids and antihistamines mimicked, to varying extents, the DAU-modulating action of L-histidinol. These data suggest that the selective modulation of DAU toxicity by L-histidinol invoves both inhibition of protein synthesis and unknown action(s) attributable to its imidazole moiety and that other pharmacological agents are modulators of anticancer drug toxicity.