The role of alkalizing and neutral potassium salts in urinary bladder carcinogenesis in rats.
Using an initiation-promotion rat model, we have previously shown that the alkalizing salt KHCO3 is a strong and the neutral salt KCl a weak promoter of urinary bladder carcinogenesis. We have now studied the effects of these salts on rat urinary bladder epithelium without prior exposure to a bladder tumour initiator. In four studies ranging in duration from 4 to 130 weeks, (equimolar) amounts of K+ were administered in the diet to male and female rats (85 rats/sex/group) as KHCO3 or KCl. Comparable increases in urinary volume and potassium levels were found with both KHCO3 and KCl, but only KHCO3 induced an elevated urinary pH. The feeding of KHCO3 resulted in simple epithelial hyperplasia and, after prolonged administration, in papillary/nodular hyperplasia, papillomas and transitional cell carcinomas of the urinary bladder. With KCl, only a slight increase in proliferative urothelial lesions was found; one male showed papillary hyperplasia and one female exhibited nodular hyperplasia and a papilloma. Our results allow the conclusion that KHCO3, a strong promoter of bladder carcinogenesis, is capable of inducing urinary bladder cancer in rats without prior application of an initiator, whereas KCl, a weak tumour promoter, induced only a few (pre)neoplastic lesions.
Lina
B A
BA
TNO-Toxicology and Nutrition Institute, Zeist, The Netherlands.
Hollanders
V M
VM
Kuijpers
M H
MH
D000818:Animals; D001639:Bicarbonates / Q000633:toxicity*; D005260:Female; D006863:Hydrogen-Ion Concentration; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D011189:Potassium Chloride / Q000633:toxicity*; D017680:Potassium Compounds / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*; D014556:Urine
D001639:Bicarbonates; D017680:Potassium Compounds; D011189:Potassium Chloride; C026329:potassium bicarbonate