No promotion of urinary bladder carcinogenesis by sodium L-ascorbate in male ODS/Shi-od/od rats lacking L-ascorbic acid-synthesizing ability.
The promoting effects of sodium L-ascorbate (Na-AsA) on two-stage urinary bladder carcinogenesis were investigated in male ODS/Shi-od/od rats. This strain genetically lacks L-ascorbic acid-synthesizing ability, which is controlled by a single autosomal recessive od gene; heterozygous ODS/Shi(-)+/od, normal ODS/Shi(-)+/+ or F344 rats are able to synthesize L-ascorbic acid. In experiment 1, ODS/Shi-od/od and F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 2 weeks and then basal CA-1 diet with or without 5% Na-AsA for 32 weeks. F344 rats were sensitive to the promoting effects of Na-AsA, whereas ODS/Shi-od/od rats were resistant. Administration of Na-AsA increased the urinary pH and the urinary concentrations of Na+ and total ascorbic acid in all strains. In experiment 2, DNA synthesis in the urinary bladder epithelium of F344 rats fed MF diet or CA-1 diet was increased by exposure to 5% Na-AsA for 8 weeks, but not in ODS/Shi-od/od rats fed CA-1 diet. In experiment 3, ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were given 0.05% BBN for 4 weeks and then CA-1 diet with or without 5% Na-AsA for 32 weeks. ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were resistant to the promoting effects of Na-AsA in two-stage urinary bladder carcinogenesis. The urinary pH and the urinary concentrations of Na+ and total ascorbic acid in ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were increased by the administration of Na-AsA. These results indicate that ODS/Shi-od/od rats are resistant to the promoting effects of Na-AsA in two-stage urinary bladder carcinogenesis, and that the susceptibilities of ODS/Shi-od/od rats are regulated by genes different from the gene at the od locus.
Aburahi Laboratories, Shionogi & Co. Ltd., Shiga, Japan.
S
S
Mori
T
T
Murai
Y
Y
Takeuchi
M
M
Hosono
T
T
Ohhara
S
S
Makino
Y
Y
Hayashi
M A
MA
Shibata
Y
Y
Kurata
A
A
Hagiwara
D000818:Animals; D001205:Ascorbic Acid / Q000009:adverse effects* / Q000096:biosynthesis*; D001835:Body Weight / Q000187:drug effects; D002085:Butylhydroxybutylnitrosamine; D004848:Epithelium / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology
D002085:Butylhydroxybutylnitrosamine; D012964:Sodium; D001205:Ascorbic Acid