title: Severity of promotion by sodium salts of succinic acid in rat urinary bladder carcinogenesis correlates with sodium ion concentration under conditions of equal urinary pH.
abstract: Elevation of urinary pH and Na ion concentration induced by feeding high doses of sodium salts plays a crucial role in promotion of urinary bladder carcinogenesis in male rats initially treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). In the present study, urinary bladder carcinogenesis in male F344 rats was promoted by feeding the mono- and di-sodium salts of succinic acid, and the activity was enhanced by varying urinary sodium ion concentration under conditions of equally high pH. In Experiment 1, the rats were given 0.05% BBN in their drinking water for 4 weeks and then fed basal diet containing 5% succinic acid, 5% sodium succinate (Na-Suc) or 5% di-sodium succinate (2Na-Suc) for 32 weeks. The development of carcinomas in the urinary bladder was enhanced by treatment with Na-Suc and with 2Na-Suc. 2Na-Suc induced larger urinary bladder tumors than the Na-Suc. In Experiment 2, 5% Na-Suc and/or 5% 2Na-Suc were fed to the rats for 8 weeks without prior BBN treatment. Induction of simple hyperplasia as observed by light microscopy, was greater in rats fed 2Na-Suc than Na-Suc. Increased 5-bromo-2'-deoxyuridine labeling index and alterations of the urothelial surface observed by scanning electron microscopy of the urinary bladder were similarly greater in rats fed 2Na-Suc compared to Na-Suc. In addition, there was a tendency toward increased spermidine/spermine N1-acetyltransferase activity in the urinary bladder epithelium of rats fed 5% 2Na-Suc. The results of Experiment 2 corresponded to differences in promoting activity for the different chemicals in Experiment 1. Thus, tumor growth was associated with sodium ion concentration level under conditions of equal increase of urinary pH.
authors.affiliation: First Department of Pathology, Osaka City University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Otoshi
authors.forename: H
authors.initials: H
authors.lastname: Iwata
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Murai
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: I
authors.initials: I
authors.lastname: Matsui-Yuasa
authors.forename: S
authors.initials: S
authors.lastname: Otani
authors.forename: S
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000378:metabolism* / Q000633:toxicity*; D013386:Succinates / Q000633:toxicity*; D019802:Succinic Acid; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D002273:Carcinogens; D013386:Succinates; D002085:Butylhydroxybutylnitrosamine; D012964:Sodium; D019802:Succinic Acid