Epithelia hyperplasia in the renal papilla and pelvis but not the urinary bladder of male F344 rats associated with dietary sodium phosphates after uracil exposure.
Effects of the bladder tumor promoter Na3PO4 and the non-bladder-tumor promoter NaH2PO4 on development of hyperplastic lesions of urinary bladder and renal papilla/pelvis were investigated after exposure of male F344 rats to the nongenotoxic carcinogen uracil. Animals were administered with 3.0% uracil in the diet for 4 weeks and thereafter fed 3.0% Na3PO4 or 3.0% NaH2PO4 for 32 weeks. No enhancing effect of either phosphate salt on uracil-induced proliferative lesions of urinary bladder was observed. However, the sequential treatments gave rise to enhanced development of hyperplastic lesions in the renal papilla/pelvis compared to the case with uracil alone. In addition, a small number of renal pelvic papillomas were observed in the group given Na3PO4 after uracil. These phosphate salts also induced nephrocalcinosis in the papilla/pelvis concomitant with development of renal hyperplastic lesions in this location. A sequential study revealed calculus formation and proliferative lesions in both the urinary bladder and renal papilla/pelvis after 4 weeks dietary application of uracil. After cessation, calculi disappeared and the majority of hyperplastic lesions regressed, consistent with a decrease in DNA synthesis levels. Persistence of uracil-induced epithelial hyperplasia in renal papilla/pelvis under the influence of phosphate salts might have been directly due to chronic stimulation by nephrocalcinosis in these sites.
Shibata
M A
MA
First Department of Pathology, Nagoya City University Medical School, Japan.
Sano
M
M
Shirai
T
T
Imaida
K
K
Fukushima
S
S
D000818:Animals; D004347:Drug Interactions; D004848:Epithelium / Q000187:drug effects; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D007679:Kidney Medulla / Q000187:drug effects* / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced; D007682:Kidney Pelvis / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010710:Phosphates / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D014498:Uracil / Q000494:pharmacology* / Q000633:toxicity; D016482:Urinalysis; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D010710:Phosphates; D014498:Uracil; C018279:sodium phosphate