The role of mitochondrial and plasma membrane nucleoside transporters in drug toxicity.

Many anticancer and antiviral drugs are nucleoside analogues, which interfere with nucleotide metabolism and DNA replication to produce pharmacological effects. Clinical efficacy and toxicity of nucleoside drugs are closely associated with nucleoside transporters because they mediate the transport of nucleoside drugs across biological membranes. Two families of human nucleoside transporters (equilibrative nucleoside transporters and concentrative nucleoside transporters) have been extensively studied for several decades. They are widely distributed, from the plasma membrane to membranes of organelles such as mitochondria, and the distribution differs in different tissues. In addition, they have different specificities to nucleoside drugs. The characteristics of equilibrative and concentrative nucleoside transporters affect the therapeutic outcomes achieved with anticancer and antiviral nucleoside drugs. In this review, an overview of the role of mitochondrial and plasma membrane nucleoside transporters in nucleoside drug toxicity is provided. Rational design and therapeutic application of nucleoside analogues are also discussed.