The Effects of a Single Dose of Dimethylnitrosamine in the Chinese Hamster and the Persistence of DNA Alkylation Products in Selected Tissues

The acute toxicity and carcinogenicity of dimethylnitrosamine (DMN) have been examined in the Chinese hamster (Cricetulus griseus). A single dose of 20 mg/kg or less was not acutely lethal but at 30 mg/kg only a few animals survived. Liver tumours were found in all of the animals surviving two doses of 20 mg/kg and so far, 25 months after treatment, in 80% of the animals given a single dose of 20 mg/kg. Altering the diet to sucrose lumps and 20% glucose in the drinking water ad libitum for 3 days prior to DMN treatment had only a slight effect on acute toxicity and carcinogenicity. In biochemical studies, DNA was extracted from several tissues of animals killed 9 h after DMN administration (20 mg/kg). The amounts of normal and methylated purines were determined after mild acid hydrolysis and Sephadex G-10 chromatography. The highest level of methylated bases was found in the DNA of the liver. Measurement of the persistence of methylated guanines showed that liver, kidney, and lung were able to remove the major product 7-methylguanine from DNA while none of these tissues had any capacity to remove the pro-mutagenic lesion O6-methylguanine. These results are discussed in relation to the mechanism of action and tissue specificity of alkylating carcinogens in this and other experimental animal systems.