Cell proliferation and apoptosis in renal cysts induced by streptozotocin,
alloxan and ferric-nitrilotriacetate were investigated in rats. In the kidn
eys of all treated animals dilated tubules at the cortico-medullary region,
large cysts, glomerular cysts and tubular dilation in the medullary area w
ere found. Both cell proliferation and apoptosis were increased in the epit
helium of the non-dilated tubules, in the mesangial and interstitial cells.
Cells lining the dilated tubules or cysts demonstrated apoptosis but their
proliferating activity was low. By calculating the proliferation-apoptosis
ratio we found that alloxan did not change the balance between the two mec
hanisms. Meanwhile streptozotocin resulted in an increased apoptosis and fe
rric-nitrilotriacetate in an increased cell proliferation. p53 expression m
ight be responsible for the uncontrolled proliferation in rats treated with
ferric-nitrilotriacetate as this oncoprotein was diffusely present in tubu
lar cell nuclei. The observed apoptosis seemed to be independent of bcl-2 o
ncoprotein expression. We assume that the initial factor in such cystogenes
is should be a cellular injury due to direct toxic or to the diabetogenic e
ffect of the drugs. The latter is more likely as all the animals were hyper
glycemic and insulin treatment following administration of streptozotocin p
revented the morphologic changes.