Inhibitory effect of potassium citrate on rat renal tumors induced by N-ethyl-N-hydroxyethylnitrosamine followed by potassium dibasic phosphate.
Potassium dibasic phosphate (PDP) was administered at a concentration of 10% by weight in basal diet to unilaterally nephrectomized Wistar rats previously given 1000 ppm N-ethyl-N-hydroxyethyl-nitrosamine (EHEN) in the diet for 2 weeks. To study the effect of alkalinization on renal mineralization, some animals concomitantly received 5% potassium citrate (PC). Feeding PDP alone promoted adenomatous hyperplasias, which were regarded as preneoplastic lesions, as well as renal cell tumors in EHEN-initiated rats, whereas the addition of PC to PDP diets reduced the promoting effect. Histopathology, serum biochemistry and urinalysis indicated retardation of renal calcium crystallization by PC. Two other phosphate salts, sodium phosphate (SP) and calcium phosphate (CP), were also administered. SP showed a slight promoting effect on adenomatous hyperplasias and a 2-fold increase in the yield of renal cell tumors, while CP induced a clear reduction of both lesions, over EHEN alone. The promoting effects of both PDP and SP and the inhibitory effect of PC were somewhat correlated to 5-bromo-2'-deoxyuridine labeling indices, the degree of nephropathy, and mineralization in the kidney. Immunohistochemically, the nephropathy induced by phosphate salts was not linked to alpha 2u-globulin. A pathogenesis for renal carcinogenesis is suggested in which nephropathy associated with mineralization enhances the development of renal cell tumors.
Konishi
N
N
Second Department of Pathology, Nara Medical University.
Nishii
K
K
Hayashi
I
I
Nakaoka
S
S
Matsumoto
K
K
Yabuno
T
T
Kitahori
Y
Y
Hiasa
Y
Y
D000510:Alpha-Globulins / Q000032:analysis; D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D004052:Diethylnitrosamine / Q000031:analogs & derivatives*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009929:Organ Size; D010710:Phosphates / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D017680:Potassium Compounds; D051381:Rats; D017208:Rats, Wistar
D000510:Alpha-Globulins; D002951:Citrates; D010710:Phosphates; D017680:Potassium Compounds; C013803:alpha 2u globulin; C023845:N-ethyl-N-hydroxyethylnitrosamine; D019343:Citric Acid; D004052:Diethylnitrosamine; C013216:potassium phosphate; D011188:Potassium; D002118:Calcium