No promotion of urinary bladder carcinogenesis by sodium L-ascorbate in male ODS/Shi-od/od rats lacking L-ascorbic acid-synthesizing ability

Abstract

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.