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© 1991 Oxford University Press

research-article

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

Satoru Mori 1 2, Takashi Murail 1 3, Yasuyoshi Takeuchi 1, Motoko Hosono 1, Tadao Ohhara 1, Susumu Makino 1, Yoshiyuki Hayashi 1, Masa-Aki Shibata 2, Yasushi Kurata 2, Akihiro Hagiwara 2 and Shoji Fukushima 2

1Aburahi Laboratories, Shionogi Research Laboratories Shionogi & Co. Ltd, Koka-cho, Shiga 520-34, Japan
2First Department of Pathology, Nagoya City University Medical School Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan
3First Department of Pathology, Osaka City University Medical School Asahi-machi, Abcno-ku, Osaka 545, Japan

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-hydroxy-butyl)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 o 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.


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