Abstract
Summary
Gastric intubation of 1500 mg dimethylamine·HCl (DMA·HCl) plus 125 mg NaNO2/kg produced severe liver necrosis and an elevation of serum glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase levels. These effects, which are attributed to in vivo formation of dimethylnitrosamine (DMN), were completely prevented by simultaneous intubation of sodium ascorbate at doses of 90-720 mg/kg. A dose–response study on DMN indicated that apparent DMN yield in the DMA plus nitrite experiment was at least 40 mg/kg, and that the ascorbate reduced this yield to at most 10 mg/kg. Ascorbate (360 mg/kg) had no effect on the action of DMN itself and did not react in vitro with DMA, so that its effect was probably due to reaction with the nitrite. The results support our suggestion that ascorbate might be administered together with readily nitrosatable drugs, to inhibit possible in vivo formation of N-nitroso compounds.
We thank Drs. P. Issenberg and L. Wallcave for useful discussions and Miss Kay Devish for technical assistance. The study was supported by Contract PH 43-68-959 with the National Cancer Institute and Grant BC-39 from the American Cancer Society.
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