L-HISTIDINOL SELECTIVELY MODULATES DAUNOMYCIN TOXICITY IN NORMAL AND TUMORIGENIC KIDNEY EPITHELIAL-CELLS

L-Histidinol protects normal cells from anticancer drugs while enhanci ng the ability of these agents to eradicate tumor cells. We now report that this attribute, previously documented in normal and turner cells of fibroblastic or myeloid origin, extends to epithelial lines. Clono genic cell survival assays showed that L-histidinol protected the norm al Madin-Darby canine kidney (MDCK) epithelial cell line from daunomyc in (DAU) toxicity, brit enhanced DAU toxicity in IMDCK-T1, a tumorigen ic derivative of MDCK. The protection of MDCK cells from DAU by L-hist idinol was improved by increasing L-histidine in the media, a conditio n known to diminish L-histidinol's capacity to inhibit protein synthes is. In contrast, similar conditions markedly diminished the capacity o f L-histidinol to enhance DAU killing of MDCK-T1 cells. These data sug gest that the differential effects of L-histidinol an DAU toxicity can not be attributed totally to its ability to inhibit protein synthesis.