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):3635-9.
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.
在随附的出版物中表明，L-组氨醇可保护正常的麦迪逊-达比犬肾（MDCK）上皮细胞系免受柔红霉素（DAU）毒性的影响，但在MDCK-T1（MDCK的一种致瘤衍生物）中会增强DAU毒性。L-组氨醇对MDCK细胞免受DAU的保护作用也被证明与其抑制蛋白质合成的能力无关。在此，克隆形成细胞存活试验表明，咪唑在保护MDCK细胞免受DAU影响方面与L-组氨醇一样有效，但对MDCK-T1细胞系的影响较小。某些抗类二十烷酸药物和抗组胺药在不同程度上模拟了L-组氨醇对DAU的调节作用。这些数据表明，L-组氨醇对DAU毒性的选择性调节涉及蛋白质合成的抑制以及归因于其咪唑部分的未知作用，并且其他药理剂是抗癌药物毒性的调节剂。
