EFFECTS OF SHORT-CHAIN FATTY-ACIDS ON PRIMARY UROTHELIAL CELLS IN CULTURE - IMPLICATIONS FOR INTRAVESICAL USE IN ENTEROCYSTOPLASTIES

The presence of inflammatory changes and mucopus production in an ente rocystoplasty may be similar to the condition of diversion colitis and starvation diarrhea caused by a lack of luminal short-chain fatty aci ds (SCFAs). We postulate a therapeutic role for intravesical SCFA, Bec ause this treatment will also contact the urothelium, we have assessed the effect on cellular proliferation by utilizing primary urothelial cells in culture. Primary urothelial cells were grown from biopsy samp les of normal urothelium obtained intraoperatively. A cocktail of SCFA used in the treatment of diversion colitis was incubated with these c ells for time intervals ranging from 30 minutes to 72 hours at drug co ncentrations ranging from 0.04 to 20 mmol/L butyrate equivalent (BE), The (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) a ssay was used to measure the residual viable biomass to assess growth inhibition, These experiments were repeated on cells grown on matrigel substrate. The human urothelial cancer line RT112 was likewise expose d to SCFAs to assess selectivity between primary and transformed cells . Primary urothelial cells in culture undergo growth inhibition when e xposed to SCFAs, The concentration of SCFAs required to reduce the gen eral biomass by 50% or more (IC greater than or equal to 50) was 20 mm ol/L BE when exposure was for 2 hours or less, When drug exposure was prolonged for 72 hours, the IC greater than or equal to 50 was 2.5 mmo l/L BE. Cells grown on matrigel had their growth similarly inhibited. The IC greater than or equal to 50 for the RT112 cell line was 2.5 mmo l/L BE after 72 hours of drug incubation. Primary urothelial cells in culture undergo a time- and dose-dependent growth inhibition when expo sed to SCFAs. This inhibition is particularly apparent at the higher d oses similar to those in use in clinical practice. Cells grown on a ma trigel substrate suffer growth attenuation similar to that affecting c ells grown on polystyrene plates. In vivo assessment in a rodent intra vesical model is advisable before considering instillations in patient s.