Warrington R C, Fang W D, Zhang L, Shieh M, Saier M H
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Anticancer Res. 1996 Nov-Dec;16(6B):3629-33.
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.
L-组氨醇可保护正常细胞免受抗癌药物的影响，同时增强这些药物根除肿瘤细胞的能力。我们现在报告，这种先前在成纤维细胞或髓样来源的正常细胞和肿瘤细胞中记录的特性，也适用于上皮细胞系。克隆形成细胞存活试验表明，L-组氨醇可保护正常的犬肾上皮细胞系（MDCK）免受柔红霉素（DAU）的毒性影响，但增强了MDCK-T1（MDCK的致瘤衍生物）对DAU的毒性反应。通过增加培养基中的L-组氨酸来改善L-组氨醇对MDCK细胞免受DAU影响的保护作用，已知这种条件会降低L-组氨醇抑制蛋白质合成的能力。相反，类似条件显著降低了L-组氨醇增强DAU对MDCK-T1细胞杀伤作用的能力。这些数据表明，L-组氨醇对DAU毒性的不同影响不能完全归因于其抑制蛋白质合成的能力。
