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 (DAU) 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 assays 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 involves 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.
Warrington
R C
RC
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Fang
W D
WD
Zhang
L
L
Shieh
M
M
Saier
M H
MH
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D015777:Eicosanoids / Q000037:antagonists & inhibitors*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006641:Histidinol / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D015777:Eicosanoids; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D011500:Protein Synthesis Inhibitors; D006641:Histidinol; D003630:Daunorubicin