Ochratoxin A (OTA) is considered to be a possible human urinary tract
carcinogen, based largely on a rat model, but no molecular genetic changes in the rat
carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker
indicating activity of the mammalian target of rapamycin, which is a serine/threonine
kinase with a key role in protein biosynthesis, cell proliferation, transcription, cellular
metabolism and apoptosis, while being functionally deregulated in cancer. To assess p-S6
expression we performed immunohistochemistry on formalin-fixed and paraffin-embedded
tumours and normal tissues. Marked intensity of p-S6 expression was observed in highly
proliferative regions of rat renal carcinomas and a rare angiosarcoma, all of which were
attributed to prolonged exposure to dietary OTA. Only very small OTA-generated renal
adenomas were negative for p-S6. Examples of rat subcutaneous fibrosarcoma and
testicular seminoma, as well as of normal renal tissue, showed no or very weak positive staining. In contrast to the animal model, human renal cell carcinoma, upper urinary tract
transitional cell carcinoma from cases of Balkan endemic nephropathy, and a human
angiosarcoma were negative for p-S6. The combined findings are reminiscent of
constitutive changes in the rat tuberous sclerosis gene complex in the Eker strain correlated
with renal neoplasms, Therefore rat renal carcinogenesis caused by OTA does not
obviously mimic human urinary tract tumourigenesis.