Lack of promotion of urinary bladder carcinogenesis by sodium bicarbonate and/or l-ascorbic acid in male ODS/Shi- od/od rats synthesizing α2 μ-globulin but not l-ascorbic acid

Abstract

The study was designed to investigate whether sodium bicarbonate (NaHCO 3) and/or l-ascorbic acid (AsA) promote urinary bladder carcinogenesis in male ODS/Shi- od/od (ODS) rats, which, unlike male F344 rats, are resistant to sodium L-ascorbate (Na-AsA)-promoting effects. Whereas F344 rats can synthesize AsA and α 2 μ -globulin (A 2μ-G), only A 2μ-G is produced in ODS rats. The two strains were given 0.05% N-butyl- N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 2 wk and then were fed basal CA-1 diet supplemented with 3% NaHCO 3 plus 5% AsA (NaHCO 3 + AsA), 3% NaHCO 3, 5% AsA, or no chemicals for 32 wk. ODS rats given BBN-NaHCO 3 or BBN-(NaHCO 3 + AsA) had only a few small carcinomas in the urinary bladder, like those receiving BBN alone or BBN-AsA. In contrast, F344 rats administered BBN-NaHCO 3 or BBN-(NaHCO 3 + AsA) had many more, larger, carcinomas than animals of the same strain given BBN alone or BBN-AsA. AsA alone did not have any effect in either strain. Administration of NaHCO 3 alone or NaHCO 3 + AsA was associated with significant elevation of urinary pH and Na + concentration to the same extent in both strains but, again, AsA alone was without effect. NaHCO 3 + AsA and AsA alone increased the urinary concentration of total ascorbic acid in both strains but the observed levels were lower in ODS rats. The results indicate that ODS rats are resistant to the modifying effects of NaHCO 3 and/or AsA on two-stage urinary bladder carcinogenesis, and thus that the susceptibility to the promotional activity of sodium-salt-type compounds may be regulated by factors other than A 2μ-G-synthesizing ability and urinary levels of pH, Na + and total ascorbic acid.