Characterization of nucleobase-specific transport in human leukemic K562 cells

Number of tissues including hematopoietic and intestinal epithelial cells are deficient in de novo nucleotide synthetic pathways and rely on the salvage of exogenous nucleobases or nucleosides to maintain nucleotide pools and to meet their metabolic demands. Although the nucleoside transporters have been identified and characterized, nucleobase transporters are not identified in mammalian. This study examined guanine transport in human leukemic K562 cell line, since it is able to undergo erythroid differentiation in vitro and guanine, guanosine and guanine ribonucleotides are effective inducer of K562 cell differentiation. Uptake of. guanine by K562 cells was time- and concentration-dependent. Kinetic analysis of guanine transport revealed the involvement of two transport systems with Km values of 0.016 muM and 0.90 muM. Guanine uptake was significantly inhibited by other purine nucleobases or nucleoside, whereas pyrimidine nucleobases and nucleosides were less inhibitory. In addition, the transport activities were suppressed after differentiation with 1 mM butyrate. In conclusion, it was suggested that there are multiple purine-selective nucleobase transporters in K562 cells and they may be involved erythrocyte differentiation.