L-histidinol selectively modulates daunomycin toxicity in normal and tumorigenic kidney epithelial cells.
L-Histidinol protects normal cells from anticancer drugs while enhancing the ability of these agents to eradicate tumor cells. We now report that this attribute, previously documented in normal and tumor cells of fibroblastic or myeloid origin, extends to epithelial lines. Clonogenic cell survival assays showed 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 improved by increasing L-histidine in the media, a condition known to diminish L-histidinol's capacity to inhibit protein synthesis. In contrast, similar conditions markedly diminished the capacity of L-histidinol to enhance DAU killing of MDCK-T1 cells. These data suggest that the differential effects of L-histidinol on DAU toxicity cannot be attributed totally to its ability to inhibit protein synthesis.
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 / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006641:Histidinol / Q000494:pharmacology*; D010641:Phenotype; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D011500:Protein Synthesis Inhibitors; D006641:Histidinol; D003630:Daunorubicin