Combined effects of L-ascorbic acid, citric acid or their sodium salts on tumor induction by N-butyl-N-(4-hydroxybutyl)nitrosamine or N-ethyl-N-(4-hydroxybutyl)nitrosamine in the rat urinary bladder.
L-Ascorbic acid, citric acid or their sodium salts (at levels equivalent to 5% sodium L-ascorbate) were fed in the diet simultaneously with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) or N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) (0.025% BBN or 0.021% EHBN) in the drinking water to male F344 rats for 20 weeks to determine whether urinary pH changes affect the carcinogenicity of BBN or EHBN. In the urine, pH was decreased in rats fed the acidic chemicals and increased in rats fed their corresponding sodium salts. Histopathologically, the incidences and numbers of preneoplastic and neoplastic lesions in groups treated with each test chemical were not different from those in control groups except for sodium citrate-treated groups in which induction of carcinomas was higher, resulting from increased intake of either carcinogen and also from increased urinary excretion of main carcinogenic metabolites. These results show that the test chemicals do not affect the carcinogenicity of BBN or EHBN on the rat urinary bladder when simultaneously administered despite significant differences in urinary pH.
Inoue
T
T
First Department of Pathology, Nagoya City University Medical School, Japan.
Imaida
K
K
Suzuki
E
E
Okada
M
M
Fukushima
S
S
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity* / Q000652:urine; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D004052:Diethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity / Q000652:urine; D004347:Drug Interactions; D006863:Hydrogen-Ion Concentration; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000652:urine
D002951:Citrates; D009602:Nitrosamines; C023845:N-ethyl-N-hydroxyethylnitrosamine; D019343:Citric Acid; D002085:Butylhydroxybutylnitrosamine; D004052:Diethylnitrosamine; D001205:Ascorbic Acid