Induction of Unscheduled DNA Synthesis in Primary Human

Ochratoxin A (OTA) is a widespread contaminant in human staple food. Exposure of humans to this mycotoxin is a matter of concern because OTA is a known rodent carcinogen. As the urothelium is one target tissue of this mycotoxin, primary cultured human urothelial cells (HUC) from adults and children were used to analyze the induction of unscheduled DNA synthesis (UDS) by OTA. HUC were isolated from the ureters or renal pelves of two nephrectomized adults and of two children with ureteropelvic junction stenosis and cultured under serum-free conditions. After a confluency of 70–80 % was reached, cell proliferation was suppressed by arginine-deficient me-dium (ADM), and UDS was assessed autoradiographically by 3H-thymidine incorporation upon exposure to OTA (10–2000 nM), ethyl methanesulfonate (EMS, 5 mM, positive control), or dimethyl sulfox-ide (DMSO, 0.2%, solvent control). In control cultures the level of UDS was low. Exposure to EMS resulted in an induction of UDS (2