The polyspecific organic cation transporters OCT1 (SLC22A1), OCT2 (SLC22A2) and 
OCT3 (SLC22A3) mediate facilitated and bidirectional diffusion of small (< or = 
500Da) organic cations with broad specificities for endogenous substrates such 
as choline, acetylcholine and monoamine neurotransmitters, as well as a variety 
of xenobiotics. Importantly, besides a wide range of clinically used drugs, 
these also include several toxins like the neurotoxin 
1-methyl-4-phenylpyridinium (MPP(+)) and herbicide paraquat. OCT2-OCT-3 display 
differential tissue distribution: OCT1 is predominantly found in liver of 
humans, and liver and kidney in rodents; OCT2 is most strongly expressed in both 
human and rodent kidney, whereas is OCT3 primarily expressed in placenta, but 
also more widely detected in various tissues, including brain and lung. The 
physiological roles of OCTs as transporters for biogenic amines or acetylcholine 
in these tissues are still debated, in contrast to their involvement in 
providing access pathways for harmful/toxic cationic substrates into the body 
and particular tissues. This review highlights a novel role of human and rodent 
OCTs as carriers of the toxic fluorescent dye ethidium, as opposed to the less 
harmful related phenanthridine compound propidium, which is not transported. 
Additional uptake and efflux pathways for ethidium in pro- and eukaryotes are 
discussed. OCT-mediated pathways may determine major entry routes for ethidium 
into the body where toxicity via specific mechanisms may develop in tissues 
expressing OCTs. Considering the high affinity of OCTs for ethidium (K(m) = 1-2 
microM) and their strong expression in various organs, strict safety guidelines 
for the handling of ethidium should be reinforced.