title: 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.
abstract: 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.
authors.affiliation: First Department of Pathology, Nagoya City University Medical School, Japan.
authors.forename: M A
authors.initials: MA
authors.lastname: Shibata
authors.forename: M
authors.initials: M
authors.lastname: Sano
authors.forename: T
authors.initials: T
authors.lastname: Shirai
authors.forename: K
authors.initials: K
authors.lastname: Imaida
authors.forename: S
authors.initials: S
authors.lastname: Fukushima
mesh_terms: 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
chemical_list: D010710:Phosphates; D014498:Uracil; C018279:sodium phosphate